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Immune reconstitution in children following chemotherapy for Acute Lymphoblastic Leukaemia

Immune reconstitution in children following chemotherapy for Acute Lymphoblastic Leukaemia
Immune reconstitution in children following chemotherapy for Acute Lymphoblastic Leukaemia
Although survival rates for paediatric Acute Lymphoblastic Leukaemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long-term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at 6 time points, during and for 18-months following treatment, with 30-39 patients analysed at each time point.

Total lymphocytes were reduced during maintenance chemotherapy and remained low 18-months following treatment completion. CD4 T cells remained significantly reduced 18-months after treatment, but CD8 cells and natural killer cells recovered to normal values. The fall in naïve B cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B-cells, particularly non class-switched memory B-cells, remained below normal levels 18 months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected.

This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B-cell numbers recover rapidly, disruption of memory/naïve balance persists and T cell compartment persist at 18-months. This highlights the impact of modern chemotherapy regimens on immunity, and thus infectious susceptibility and response to immunisation. Although survival rates for paediatric Acute Lymphoblastic Leukaemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long-term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at 6 time points, during and for 18-months following treatment, with 30-39 patients analysed at each time point.

Total lymphocytes were reduced during maintenance chemotherapy and remained low 18-months following treatment completion. CD4 T cells remained significantly reduced 18-months after treatment, but CD8 cells and natural killer cells recovered to normal values. The fall in naïve B cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B-cells, particularly non class-switched memory B-cells, remained below normal levels 18 months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected.

This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B-cell numbers recover rapidly, disruption of memory/naïve balance persists and T cell compartment persist at 18-months. This highlights the impact of modern chemotherapy regimen
Williams, Anthony
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Bate, Jessica
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Brooks, Rachel
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Clarke, Stuart
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Dixon, Elizabeth
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Faust, Saul
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Chisholm, Julia C.
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Galanopoulou, Angeliki
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Heath, Paul
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Maishman, Thomas
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Mapstone, Susan
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Patel, Soonie R.
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Vora, Ajay
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Wilding, Sam
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Gray, Juliet
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Williams, Anthony
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Bate, Jessica
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Brooks, Rachel
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Clarke, Stuart
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Dixon, Elizabeth
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Faust, Saul
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Chisholm, Julia C.
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Galanopoulou, Angeliki
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Heath, Paul
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Maishman, Thomas
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Mapstone, Susan
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Patel, Soonie R.
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Vora, Ajay
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Wilding, Sam
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Gray, Juliet
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Williams, Anthony, Bate, Jessica, Brooks, Rachel, Clarke, Stuart, Dixon, Elizabeth, Faust, Saul, Chisholm, Julia C., Galanopoulou, Angeliki, Heath, Paul, Maishman, Thomas, Mapstone, Susan, Patel, Soonie R., Vora, Ajay, Wilding, Sam and Gray, Juliet (2020) Immune reconstitution in children following chemotherapy for Acute Lymphoblastic Leukaemia. ejHaem. (doi:10.1002/jha2.27).

Record type: Article

Abstract

Although survival rates for paediatric Acute Lymphoblastic Leukaemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long-term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at 6 time points, during and for 18-months following treatment, with 30-39 patients analysed at each time point.

Total lymphocytes were reduced during maintenance chemotherapy and remained low 18-months following treatment completion. CD4 T cells remained significantly reduced 18-months after treatment, but CD8 cells and natural killer cells recovered to normal values. The fall in naïve B cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B-cells, particularly non class-switched memory B-cells, remained below normal levels 18 months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected.

This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B-cell numbers recover rapidly, disruption of memory/naïve balance persists and T cell compartment persist at 18-months. This highlights the impact of modern chemotherapy regimens on immunity, and thus infectious susceptibility and response to immunisation. Although survival rates for paediatric Acute Lymphoblastic Leukaemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long-term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at 6 time points, during and for 18-months following treatment, with 30-39 patients analysed at each time point.

Total lymphocytes were reduced during maintenance chemotherapy and remained low 18-months following treatment completion. CD4 T cells remained significantly reduced 18-months after treatment, but CD8 cells and natural killer cells recovered to normal values. The fall in naïve B cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B-cells, particularly non class-switched memory B-cells, remained below normal levels 18 months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected.

This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B-cell numbers recover rapidly, disruption of memory/naïve balance persists and T cell compartment persist at 18-months. This highlights the impact of modern chemotherapy regimen

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Accepted/In Press date: 20 May 2020
e-pub ahead of print date: 10 June 2020

Identifiers

Local EPrints ID: 441098
URI: http://eprints.soton.ac.uk/id/eprint/441098
PURE UUID: ec9f3e8a-1ea4-4d64-8812-ad1bd815302a
ORCID for Stuart Clarke: ORCID iD orcid.org/0000-0002-7009-1548
ORCID for Saul Faust: ORCID iD orcid.org/0000-0003-3410-7642
ORCID for Sam Wilding: ORCID iD orcid.org/0000-0003-4184-2821
ORCID for Juliet Gray: ORCID iD orcid.org/0000-0002-5652-4722

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Date deposited: 01 Jun 2020 16:30
Last modified: 18 Feb 2021 17:33

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