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. 2020 Jun 10;1(1):142-151.
doi: 10.1002/jha2.27. eCollection 2020 Jul.

Immune reconstitution in children following chemotherapy for acute leukemia

Anthony P Williams  1 , Jessica Bate  2 , Rachael Brooks  1 , Julia Chisholm  3 , Stuart C Clarke  1 , Elizabeth Dixon  4 , Saul N Faust  1 , Angeliki Galanopoulou  4 , Paul T Heath  5 , Thomas Maishman  4 , Susan Mapstone  2 , Soonie R Patel  6 , Ajay Vora  7 , Sam A Wilding  4 , Juliet C Gray  1   2
Affiliations

Immune reconstitution in children following chemotherapy for acute leukemia

Anthony P Williams et al. EJHaem. .

Abstract

Although survival rates for pediatric acute lymphoblastic leukemia 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 six time points, during and for 18-month following treatment, with 30-39 patients analyzed 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 nonclass-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 immunization.

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Figures

FIGURE 1
FIGURE 1
Total lymphocyte and total B‐cell counts during and after treatment. Boxplot showing total lymphocyte (blue) and total B‐cell (CD19+, red) counts at each time point relative to chemotherapy, as percentage of the median of healthy children. Lines within the boxes represent medians and diamonds represent means
FIGURE 2
FIGURE 2
Naïve and memory B‐cell counts during and after treatment. Boxplot showing naïve B cells (blue) and class switched (CD27+IgM/D‐, red) and nonclass switched (CD27+IgM/D+, green) memory B cells. Lines within the boxes represent medians and diamonds represent means (red) and unstitched memory (green). Cell count as a percentage of the median of healthy children, at each time point relative to chemotherapy. Lines within the boxes represent medians and diamonds represent means
FIGURE 3
FIGURE 3
CD4 and CD8 T‐cell counts during and after treatment. Boxplots showing: (A) CD4+ve and (B) CD8+ve T‐cell counts as a percentage of the median of healthy children by time relative to chemotherapy. Lines within the boxes represent medians and diamonds represent means
FIGURE 4
FIGURE 4
Comparison of different chemotherapy regimens. Bar graphs showing (A) Mean total lymphocyte count percentage of the median of healthy children by chemotherapy regimen. (B) Mean total B‐cells (CD19+) percentage of the median of healthy children by chemotherapy regimen. Lines represent the confidence limits of the means
FIGURE 5
FIGURE 5
Comparison of immune effects of treatment in boys and girls. Bar graphs showing (A) Mean total lymphocyte count percentage of the median of healthy children by chemotherapy regimen. (B) Mean total B‐cells (CD19+) percentage of the median of healthy children by gender. Lines represent the confidence limits of the means
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