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High pre-harvest donor Foxp3 mRNA level predicts late relapse of acute lymphoblastic leukaemia after haematopoietic stem cell transplantation

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@article{9b7373fb76274c4394973afbe122739b,
title = "High pre-harvest donor Foxp3 mRNA level predicts late relapse of acute lymphoblastic leukaemia after haematopoietic stem cell transplantation",
abstract = "OBJECTIVES: The curative effect of allogeneic haematopoietic stem cell transplantation (HSCT) for acute leukaemia is due in part to the donor T cell-mediated graft-versus-leukaemia immune reaction (GvL). Several studies have suggested that donor CD25+CD4+Foxp3+ regulator T cells (Tregs) may decrease graft-versus-host disease (GvHD) without abrogating GVL. This notion may need modification in acute lymphoblastic leukaemia (ALL).METHODS: Foxp3 mRNA level was measured by qPCR in pre-harvest donor blood CD4+ T cells. The study comprised 45 patients with ALL in 1st or 2nd CR who received myeloablative HSCT using T-replete bone marrow grafts.RESULTS: Relapse occurred in 17 patients median 363 days after HSCT. The relapse risk was estimated by Cox univariate and multivariate proportional hazard regression. The proportionality assumption was met by analysing the pre-harvest donor Foxp3 mRNA level as a time-dependent covariate. Early relapse was not modified by the Foxp3 mRNA level. However, a higher Foxp3 mRNA level was associated with a significantly increased relapse risk after day 363 after transplantation, compatible with inhibition of GvL. In contrast, a higher pre-harvest donor CD4+ T cell concentration was associated with reduced relapse risk.CONCLUSION: A higher pre-harvest donor Foxp3 mRNA level may be predictive of late ALL relapse after HSCT.",
keywords = "acute lymphoblastic leukaemia, Foxp3, haematopoietic stem cell transplantation, regulatory T cells",
author = "Niels Jacobsen and Tina Frisch and Niels Keiding and Carsten Heilmann and Henrik Sengel{\o}v and Madsen, {Hans O} and Hanne Marquart and Ebbe Dickmeiss and Andersen, {Mette K} and Christiansen, {Claus B} and Ryder, {Lars P}",
note = "{\textcopyright} 2021 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.",
year = "2021",
month = may,
doi = "10.1111/ejh.13591",
language = "English",
volume = "106",
pages = "643--653",
journal = "European Journal of Haematology",
issn = "0902-4441",
publisher = "Wiley-Blackwell Munksgaard",
number = "5",

}

RIS

TY - JOUR

T1 - High pre-harvest donor Foxp3 mRNA level predicts late relapse of acute lymphoblastic leukaemia after haematopoietic stem cell transplantation

AU - Jacobsen, Niels

AU - Frisch, Tina

AU - Keiding, Niels

AU - Heilmann, Carsten

AU - Sengeløv, Henrik

AU - Madsen, Hans O

AU - Marquart, Hanne

AU - Dickmeiss, Ebbe

AU - Andersen, Mette K

AU - Christiansen, Claus B

AU - Ryder, Lars P

N1 - © 2021 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.

PY - 2021/5

Y1 - 2021/5

N2 - OBJECTIVES: The curative effect of allogeneic haematopoietic stem cell transplantation (HSCT) for acute leukaemia is due in part to the donor T cell-mediated graft-versus-leukaemia immune reaction (GvL). Several studies have suggested that donor CD25+CD4+Foxp3+ regulator T cells (Tregs) may decrease graft-versus-host disease (GvHD) without abrogating GVL. This notion may need modification in acute lymphoblastic leukaemia (ALL).METHODS: Foxp3 mRNA level was measured by qPCR in pre-harvest donor blood CD4+ T cells. The study comprised 45 patients with ALL in 1st or 2nd CR who received myeloablative HSCT using T-replete bone marrow grafts.RESULTS: Relapse occurred in 17 patients median 363 days after HSCT. The relapse risk was estimated by Cox univariate and multivariate proportional hazard regression. The proportionality assumption was met by analysing the pre-harvest donor Foxp3 mRNA level as a time-dependent covariate. Early relapse was not modified by the Foxp3 mRNA level. However, a higher Foxp3 mRNA level was associated with a significantly increased relapse risk after day 363 after transplantation, compatible with inhibition of GvL. In contrast, a higher pre-harvest donor CD4+ T cell concentration was associated with reduced relapse risk.CONCLUSION: A higher pre-harvest donor Foxp3 mRNA level may be predictive of late ALL relapse after HSCT.

AB - OBJECTIVES: The curative effect of allogeneic haematopoietic stem cell transplantation (HSCT) for acute leukaemia is due in part to the donor T cell-mediated graft-versus-leukaemia immune reaction (GvL). Several studies have suggested that donor CD25+CD4+Foxp3+ regulator T cells (Tregs) may decrease graft-versus-host disease (GvHD) without abrogating GVL. This notion may need modification in acute lymphoblastic leukaemia (ALL).METHODS: Foxp3 mRNA level was measured by qPCR in pre-harvest donor blood CD4+ T cells. The study comprised 45 patients with ALL in 1st or 2nd CR who received myeloablative HSCT using T-replete bone marrow grafts.RESULTS: Relapse occurred in 17 patients median 363 days after HSCT. The relapse risk was estimated by Cox univariate and multivariate proportional hazard regression. The proportionality assumption was met by analysing the pre-harvest donor Foxp3 mRNA level as a time-dependent covariate. Early relapse was not modified by the Foxp3 mRNA level. However, a higher Foxp3 mRNA level was associated with a significantly increased relapse risk after day 363 after transplantation, compatible with inhibition of GvL. In contrast, a higher pre-harvest donor CD4+ T cell concentration was associated with reduced relapse risk.CONCLUSION: A higher pre-harvest donor Foxp3 mRNA level may be predictive of late ALL relapse after HSCT.

KW - acute lymphoblastic leukaemia

KW - Foxp3

KW - haematopoietic stem cell transplantation

KW - regulatory T cells

U2 - 10.1111/ejh.13591

DO - 10.1111/ejh.13591

M3 - Journal article

C2 - 33527553

VL - 106

SP - 643

EP - 653

JO - European Journal of Haematology

JF - European Journal of Haematology

SN - 0902-4441

IS - 5

ER -

ID: 62112730