Impact of CAR T cell therapy on thymus size in children and young adults with acute lymphoblastic leukemia

Abstract

Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated efficacy in children and young adult patients with acute lymphoblastic leukemia (ALL). The purpose of our study was to investigate thymus size changes after CAR T-cell therapy, explore the associated clinical conditions, and assess survival differences of patients who underwent CAR T-cell therapy, we conducted a single-center retrospective study of children and young adult patients who underwent CAR T-cell therapy for ALL between April 2015 and October 2023.We measured the volume of the thymus on pre- and post-CAR T-cell chest CT scans of 20 patients (median [IQR] age, 18[11] years; 11 females). We divided patients into two groups, those who did (group 1) or did not (group 2) demonstrate increase in thymus size after therapy. Clinical and survival data were collected. We used the Wilcoxon signed-rank test or Fisher's exact test for group comparisons and analyzed event-free survival data. Seven of 20 patients (35%, group 1) showed increase in thymus volume (pre- vs. post-CAR T-cell thymus volume; 5.01 [2.18] cm³ vs. 20.87 [19.86] cm³, p = 0.01), while 13 patients (65%, group 2) showed no increase in thymus volume (pre- vs. post-CAR T-cell thymus volume; 3.01 [13.42] cm³ vs. 2.09 [8.34] cm³, p = 0.01). Patients in group 1 were younger (12 [8] years vs. 19[10] years, p = 0.028) and showed a higher rate of event-free survival compared to those in group 2 (p = 0.003). In children and young adults with ALL, increased thymus size after CAR T-cell therapy was associated with younger age and improved clinical outcomes.

Keywords: CAR T-cell therapy; Chest CT; Child; Event-free survival; Leukemia; Thymus.

Fig. 1

Flow chart of patient’s selection.

Fig. 2

Timeline figure of 20 patients showing the relative time interval (days) between chest computed tomography (CT) and therapies in relation to the CAR T-cell infusion date.

Fig. 3

Axial chest computed tomography (CT) images of a 9-year-old male patient with B-ALL pre- and post-CAR T-cell therapy. a) An axial chest CT image pre-CAR T-cell therapy shows the initial size and shape of the thymus. The thymus presents as triangular tissue in the anterior mediastinal region and does not cause any mass effect on adjacent vessels. b) An Axial chest CT image at 53 days post-CAR T-cell therapy shows an enlarged and more lobulated thymus. The thymus has increased in size (from 0.55cm³to 73.51cm³) and exhibits a lobulated shape with sharp, rounded margins and increased contrast enhancement.

Fig. 4

Fluoroscopic chest images from interventional radiology (IR) procedures of a 12-year-old male patient with B-ALL before and after CAR T-cell therapy. a) Frontal fluoroscopic chest image acquired during PICC line placement demonstrates a normal mediastinal contour with no evidence of thymic enlargement. b) Frontal fluoroscopic image at 32 days post-CAR T-cell shows increased prominence of the anterior mediastinal silhouette, suggesting interval thymic enlargement.

Fig. 5

Axial chest computed tomography (CT) images of an 18-year-old female patient with ALL before and after CAR T-cell therapy. a) An axial chest CT image pre-CAR T-cell therapy shows the initial size and shape of the thymus. b) An axial chest CT image 32 days post-CAR T-cell therapy shows no significant change in the size and shape of the thymus.

Fig. 6

Change in thymus size pre- and post- CAR T-cell therapy. a) In group 1, the thymus volume, as measured on chest CT, significantly increased following CAR T cell therapy, from a median of 5.01 cm³ [interquartile range, IQR: 2.64] pre-CAR T-cell therapy to a median of 20.87 cm³ [IQR: 7.83] post-CAR T-cell therapy (p=0.001). b) In group 2, the thymus volume decreased from a median of 3.1 cm³ [IQR: 8.2] pre-CAR T-cell therapy to a median of 2.9 cm³ [IQR: 5.01] post-CAR T-cell therapy (p=0.001). c) In group 1, the transverse thymic size, as measured on fluoroscopic chest images from interventional radiology procedures, increased significantly following CAR T-cell therapy, from a median of 6.96 cm [IQR: 0.75] to a median of 7.14 cm [IQR: 1.40] (p = 0.012). d) In contrast, group 2 showed no significant change in transverse thymic size on fluoroscopic chest images after CAR T-cell therapy (p = 0.699).

Fig. 7

Lymphocyte counts by flow cytometry after CAR T-cell therapy. Group 1 (patients with increased thymic size) showed higher absolute lymphocyte counts, indicating a trend toward greater immune recovery compared to Group 2 (patients without thymic size increase); however, this difference did not reach statistical significance (p = 0.081).

Fig. 8

CD4 Recent Thymic Emigrants (RTEs) by flow cytometry after CAR T-cell therapy. a) Group 1 (patients with increased thymic size) showed a higher percentage of RTEs compared to Group 2 (patients without thymic size increase; p = 0.014). b) Patients in Group 1 demonstrated significantly elevated absolute counts of CD4⁺ RTEs compared to patients from Group 2 (p = 0.032), indicating a trend towards greater thymic regenerative activity and enhanced T-cell reconstitution following therapy.

Fig. 9

Kaplan-Meier survival curves for patients with (blue line, group 1) and without (yellow dashed line, group 2) thymus enlargement after CAR T cell treatment protocol. a) Patients with thymus enlargement after CAR T-cell treatment showed prolonged survival compared to patients without thymus enlargement (p = 0.017). b) Patients with thymus enlargement after CAR T-cell treatment showed higher event-free survival compared to patients without thymus enlargement (p = 0.003).

Fig. 10

Kaplan–Meier survival curves stratified by CAR T-cell therapy type. Both overall survival and event-free survival differed significantly between therapy types (p < 0.01 and p = 0.01, respectively).