Ex vivo and in vivo T-cell depletion in allogeneic transplantation: towards less or non-cytotoxic conditioning regimens

Handgretinger, Rupert; Arendt, Anne-Marie; Maier, Claus‐Philipp; Lang, Peter

doi:10.1080/1744666x.2022.2134857

Cited by 4 publications

(2 citation statements)

References 95 publications

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“…In recent years, the safety and efficacy of both approaches has been demonstrated in children with congenital diseases 27,28,41–45 and also Fanconi Anemia, 46–49 with high survival reported. In lieu of evidence to favor one approach over the other there has been active debate overwhich approach carries more advantages 36,50…”

Section: Discussionmentioning

confidence: 99%

HLA‐haploidentical stem cell transplantation in children with inherited bone marrow failure syndromes: A retrospective analysis on behalf of EBMT severe aplastic Anemia and pediatric diseases working parties

Giardino,

Eikema,

Piepenbroek

et al. 2024

American J Hematol

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Haploidentical stem cell transplantation (haplo‐SCT) represents the main alternative for children with inherited bone marrow failure syndrome (I‐BMF) lacking a matched donor. This retrospective study, conducted on behalf of the EBMT SAAWP and PDWP, aims to report the current outcomes of haplo‐SCT in I‐BMFs, comparing the different in vivo and ex vivo T‐cell depletion approaches. One hundred and sixty‐two I‐BMF patients who underwent haplo‐SCT (median age 7.4 years) have been registered. Fanconi Anemia was the most represented diagnosis (70.1%). Based on different T‐cell depletion (TCD) approaches, four categories were identified: (1) TCRαβ+/CD19+‐depletion (43.8%); (2) T‐repleted with post‐transplant Cyclophosphamide (PTCy, 34.0%); (3) In‐vivo T‐depletion with ATG/alemtuzumab (14.8%); (4) CD34+ positive selection (7.4%). The cumulative incidences (CI) of neutrophil and platelet engraftment were 84% and 76% respectively, while that of primary and secondary graft failure was 10% and 8% respectively. The 100‐day CI of acute GvHD grade III‐IV(95% CI) was 13%, while the 24‐month CI of extensive chronic GvHD was 4%. After a median follow‐up of 43.4 months, the 2‐year overall survival(OS) and GvHD/Rejection‐free Survival (GRFS) probabilities are 67% and 53%, respectively. The TCR CD3+αβ+/CD19+ depletion group showed a significantly lower incidence of both acute and chronic GvHD and higher OS (79%; p0.013) and GRFS (71%; p < .001), while no significant differences in outcomes have been observed by different diagnosis and conditioning regimens. This large retrospective study supports the safety and feasibility of haplo‐SCT in I‐BMF patients. TCRαβ+/CD19+ depletion offers higher chances of patients' survival, with a significantly lower risk of severe a‐ and c‐GvHD in I‐BMFs compared to other platforms.

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Section: Discussionmentioning

confidence: 99%

HLA‐haploidentical stem cell transplantation in children with inherited bone marrow failure syndromes: A retrospective analysis on behalf of EBMT severe aplastic Anemia and pediatric diseases working parties

Giardino,

Eikema,

Piepenbroek

et al. 2024

American J Hematol

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“…A more predictable and measurable approach to the elimination of donor-derived T lymphocytes has been physical manipulation of the graft with depletion of T lymphocytes or its subsets and/or selection of CD34 + HSCs (23). With these processes being much refined over the last two decades, the immunomagnetic depletion of TCRab + or CD45RA + T cells from the graft remain the most common approach to graft manipulation (24).…”

Section: T-cell Depletion-one Way or The Othermentioning

confidence: 99%

Abatacept and T-cell costimulation blockade—shifting the paradigm in the prevention of graft-versus-host disease

Chakrabarti,

Jaiswal

2023

Front. Hematol.

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Despite advances in transplantation techniques and immunosuppressive therapies, graft-versus-host disease (GVHD) remains a significant cause of morbidity and mortality, necessitating the use of innovative strategies for its prevention. T-cell activation plays a crucial role in the pathogenesis of GVHD, and T-cell costimulation blockade (COSBL) has emerged as a promising approach to prevent this devastating condition. This review aims to explore the concept of COSBL and its potential as a paradigm-shifting strategy in the prevention of GVHD, in the context of the existing modalities for the prevention of GVHD and the preclinical and clinical studies on COSBL. The unique property of abatacept (CTLA4Ig) is not just limited to dampening T-cell activation. The salutary effect of abatacept on natural killer (NK) cells and Tregs alike provides a unique opportunity to dissociate T-cell-mediated GVHD from NK cell-mediated graft-versus-leukemia. Further research is warranted to explore other modalities of COSBL, determine the optimal dosing and combinations for COSBL, and identify predictive biomarkers for patient stratification, ultimately paving the way for improved outcomes in hematopoietic cell transplantation recipients.

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Minor histocompatibility antigens to predict, monitor or manipulate GvL and GvHD after allogeneic hematopoietic cell transplantation

Fuchs,

Falkenburg,

Griffioen

2024

Best Practice & Research Clinical Haematology

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Ex vivo and in vivo T-cell depletion in allogeneic transplantation: towards less or non-cytotoxic conditioning regimens

Cited by 4 publications

References 95 publications

HLA‐haploidentical stem cell transplantation in children with inherited bone marrow failure syndromes: A retrospective analysis on behalf of EBMT severe aplastic Anemia and pediatric diseases working parties

HLA‐haploidentical stem cell transplantation in children with inherited bone marrow failure syndromes: A retrospective analysis on behalf of EBMT severe aplastic Anemia and pediatric diseases working parties

Abatacept and T-cell costimulation blockade—shifting the paradigm in the prevention of graft-versus-host disease

Minor histocompatibility antigens to predict, monitor or manipulate GvL and GvHD after allogeneic hematopoietic cell transplantation

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