Allogeneic mesenchymal stromal cell therapy on primary graft dysfunction after lung transplantation

Abbas Ali Qayyum; Thomas Kromann Lund; Pia Bredahl Jensen; Kristine Jensen; Mandana Haack-Sørensen; Annette Ekblond; Morten Juhl Nørgaard; Hasse Møller-Sørensen; Anders Bruun Mathiasen; Christian Holdflod Møller; Sara Bird Rørvig; Anna Kalhauge; Helle Bruunsgaard; Thomas Litman; Ellen Mønsted Johansen; Lisbeth Drozd Højgaard; Jens Kastrup; Michael Perch

doi:10.1016/j.jhlto.2025.100254

Allogeneic mesenchymal stromal cell therapy on primary graft dysfunction after lung transplantation

Abbas Ali Qayyum^*, Thomas Kromann Lund, Pia Bredahl Jensen, Kristine Jensen, Mandana Haack-Sørensen, Annette Ekblond, Morten Juhl Nørgaard, Hasse Møller-Sørensen, Anders Bruun Mathiasen, Christian Holdflod Møller, Sara Bird Rørvig, Anna Kalhauge, Helle Bruunsgaard, Thomas Litman, Ellen Mønsted Johansen, Lisbeth Drozd Højgaard, Jens Kastrup, Michael Perch

^*Corresponding author af dette arbejde

Abstract

BACKGROUND: Primary graft dysfunction (PGD) is common in lung transplantation affecting 15-30% of recipients. It represents a multifactorial injury to the transplanted lung within the first 72 hours after transplantation.We aimed to investigate clinical safety and efficacy of allogeneic adipose tissue-derived stromal cells (ASCs), as an add-on therapy in patients undergoing double lung transplantation.

METHODS: Single center, double-blinded, investigator-initiated randomized phase I/II study with intravenous infusion of either ASCs or placebo within two hours after lung transplantation. A total of 31 patients were included and randomized 1:1:1 to either 200 million or 100 million ASCs, or placebo infusion.The primary endpoint was difference in PGD grade 72 hours after transplantation between groups.

RESULTS: No significant differences in PGD were seen between the 3 groups 72 hours after lung transplantation (P=0.426). Combined ASC groups compared to placebo group did not show any difference in PGD 72 hours after transplantation (P=0.252). A reduced progression in PGD from day 1 to day 3 and day 2 to day 3 was observed between the ASC treated patients and patients in the placebo group (P=0.034 and P=0.034, respectively). There were no significant differences in number of serious adverse events or in secondary endpoints such as kidney function, lung function, or quality-of-life between groups.

CONCLUSIONS: Intravenous infusion of allogeneic ASCs in patients immediately after double lung transplantation was safe. The therapy did not show statistic difference in PGD between groups 72 hours after lung transplantation.

CLINICAL TRIAL REGISTRATION INFORMATION: EudraCT number 2019-004848-30 and NCT04714801.

Originalsprog	Engelsk
Tidsskrift	JHLT Open
Vol/bind	8
Sider (fra-til)	100254
ISSN	2950-1334
DOI	https://doi.org/10.1016/j.jhlto.2025.100254
Status	Udgivet - maj 2025

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10.1016/j.jhlto.2025.100254Licens: CC BY-NC-ND

Citationsformater

Qayyum, A. A., Lund, T. K., Jensen, P. B., Jensen, K., Haack-Sørensen, M., Ekblond, A., Nørgaard, M. J., Møller-Sørensen, H., Mathiasen, A. B., Møller, C. H., Rørvig, S. B., Kalhauge, A., Bruunsgaard, H., Litman, T., Johansen, E. M., Højgaard, L. D., Kastrup, J., & Perch, M. (2025). Allogeneic mesenchymal stromal cell therapy on primary graft dysfunction after lung transplantation. JHLT Open, 8, 100254. https://doi.org/10.1016/j.jhlto.2025.100254

Qayyum, AA, Lund, TK, Jensen, PB , Jensen, K, Haack-Sørensen, M, Ekblond, A , Nørgaard, MJ , Møller-Sørensen, H , Mathiasen, AB , Møller, CH , Rørvig, SB , Kalhauge, A , Bruunsgaard, H, Litman, T, Johansen, EM , Højgaard, LD , Kastrup, J & Perch, M 2025, 'Allogeneic mesenchymal stromal cell therapy on primary graft dysfunction after lung transplantation', JHLT Open, bind 8, s. 100254. https://doi.org/10.1016/j.jhlto.2025.100254

@article{3dad0c25f590432fa679ac2ec88f48c8,

title = "Allogeneic mesenchymal stromal cell therapy on primary graft dysfunction after lung transplantation",

abstract = "BACKGROUND: Primary graft dysfunction (PGD) is common in lung transplantation affecting 15-30% of recipients. It represents a multifactorial injury to the transplanted lung within the first 72 hours after transplantation.We aimed to investigate clinical safety and efficacy of allogeneic adipose tissue-derived stromal cells (ASCs), as an add-on therapy in patients undergoing double lung transplantation.METHODS: Single center, double-blinded, investigator-initiated randomized phase I/II study with intravenous infusion of either ASCs or placebo within two hours after lung transplantation. A total of 31 patients were included and randomized 1:1:1 to either 200 million or 100 million ASCs, or placebo infusion.The primary endpoint was difference in PGD grade 72 hours after transplantation between groups.RESULTS: No significant differences in PGD were seen between the 3 groups 72 hours after lung transplantation (P=0.426). Combined ASC groups compared to placebo group did not show any difference in PGD 72 hours after transplantation (P=0.252). A reduced progression in PGD from day 1 to day 3 and day 2 to day 3 was observed between the ASC treated patients and patients in the placebo group (P=0.034 and P=0.034, respectively). There were no significant differences in number of serious adverse events or in secondary endpoints such as kidney function, lung function, or quality-of-life between groups.CONCLUSIONS: Intravenous infusion of allogeneic ASCs in patients immediately after double lung transplantation was safe. The therapy did not show statistic difference in PGD between groups 72 hours after lung transplantation.CLINICAL TRIAL REGISTRATION INFORMATION: EudraCT number 2019-004848-30 and NCT04714801.",

author = "Qayyum, {Abbas Ali} and Lund, {Thomas Kromann} and Jensen, {Pia Bredahl} and Kristine Jensen and Mandana Haack-S{\o}rensen and Annette Ekblond and N{\o}rgaard, {Morten Juhl} and Hasse M{\o}ller-S{\o}rensen and Mathiasen, {Anders Bruun} and M{\o}ller, {Christian Holdflod} and R{\o}rvig, {Sara Bird} and Anna Kalhauge and Helle Bruunsgaard and Thomas Litman and Johansen, {Ellen M{\o}nsted} and H{\o}jgaard, {Lisbeth Drozd} and Jens Kastrup and Michael Perch",

note = "{\textcopyright} 2025 International Society for Heart and Lung Transplantation.",

year = "2025",

month = may,

doi = "10.1016/j.jhlto.2025.100254",

language = "English",

volume = "8",

pages = "100254",

journal = "JHLT Open",

issn = "2950-1334",

publisher = "Elsevier",

}

TY - JOUR

T1 - Allogeneic mesenchymal stromal cell therapy on primary graft dysfunction after lung transplantation

AU - Qayyum, Abbas Ali

AU - Lund, Thomas Kromann

AU - Jensen, Pia Bredahl

AU - Jensen, Kristine

AU - Haack-Sørensen, Mandana

AU - Ekblond, Annette

AU - Nørgaard, Morten Juhl

AU - Møller-Sørensen, Hasse

AU - Mathiasen, Anders Bruun

AU - Møller, Christian Holdflod

AU - Rørvig, Sara Bird

AU - Kalhauge, Anna

AU - Bruunsgaard, Helle

AU - Litman, Thomas

AU - Johansen, Ellen Mønsted

AU - Højgaard, Lisbeth Drozd

AU - Kastrup, Jens

AU - Perch, Michael

PY - 2025/5

Y1 - 2025/5

N2 - BACKGROUND: Primary graft dysfunction (PGD) is common in lung transplantation affecting 15-30% of recipients. It represents a multifactorial injury to the transplanted lung within the first 72 hours after transplantation.We aimed to investigate clinical safety and efficacy of allogeneic adipose tissue-derived stromal cells (ASCs), as an add-on therapy in patients undergoing double lung transplantation.METHODS: Single center, double-blinded, investigator-initiated randomized phase I/II study with intravenous infusion of either ASCs or placebo within two hours after lung transplantation. A total of 31 patients were included and randomized 1:1:1 to either 200 million or 100 million ASCs, or placebo infusion.The primary endpoint was difference in PGD grade 72 hours after transplantation between groups.RESULTS: No significant differences in PGD were seen between the 3 groups 72 hours after lung transplantation (P=0.426). Combined ASC groups compared to placebo group did not show any difference in PGD 72 hours after transplantation (P=0.252). A reduced progression in PGD from day 1 to day 3 and day 2 to day 3 was observed between the ASC treated patients and patients in the placebo group (P=0.034 and P=0.034, respectively). There were no significant differences in number of serious adverse events or in secondary endpoints such as kidney function, lung function, or quality-of-life between groups.CONCLUSIONS: Intravenous infusion of allogeneic ASCs in patients immediately after double lung transplantation was safe. The therapy did not show statistic difference in PGD between groups 72 hours after lung transplantation.CLINICAL TRIAL REGISTRATION INFORMATION: EudraCT number 2019-004848-30 and NCT04714801.

AB - BACKGROUND: Primary graft dysfunction (PGD) is common in lung transplantation affecting 15-30% of recipients. It represents a multifactorial injury to the transplanted lung within the first 72 hours after transplantation.We aimed to investigate clinical safety and efficacy of allogeneic adipose tissue-derived stromal cells (ASCs), as an add-on therapy in patients undergoing double lung transplantation.METHODS: Single center, double-blinded, investigator-initiated randomized phase I/II study with intravenous infusion of either ASCs or placebo within two hours after lung transplantation. A total of 31 patients were included and randomized 1:1:1 to either 200 million or 100 million ASCs, or placebo infusion.The primary endpoint was difference in PGD grade 72 hours after transplantation between groups.RESULTS: No significant differences in PGD were seen between the 3 groups 72 hours after lung transplantation (P=0.426). Combined ASC groups compared to placebo group did not show any difference in PGD 72 hours after transplantation (P=0.252). A reduced progression in PGD from day 1 to day 3 and day 2 to day 3 was observed between the ASC treated patients and patients in the placebo group (P=0.034 and P=0.034, respectively). There were no significant differences in number of serious adverse events or in secondary endpoints such as kidney function, lung function, or quality-of-life between groups.CONCLUSIONS: Intravenous infusion of allogeneic ASCs in patients immediately after double lung transplantation was safe. The therapy did not show statistic difference in PGD between groups 72 hours after lung transplantation.CLINICAL TRIAL REGISTRATION INFORMATION: EudraCT number 2019-004848-30 and NCT04714801.

U2 - 10.1016/j.jhlto.2025.100254

DO - 10.1016/j.jhlto.2025.100254

M3 - Journal article

C2 - 40247997

SN - 2950-1334

VL - 8

SP - 100254

JO - JHLT Open

JF - JHLT Open

ER -

Allogeneic mesenchymal stromal cell therapy on primary graft dysfunction after lung transplantation

Abstract

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