Immune reconstitution after allogenic stem cell transplantation: An observational study in pediatric patients

Abstract

Introduction: The immune reconstitution (IR) after the allogenic hematopoietic stem cell transplantation (allo-HSCT) is a progressive process intrinsically correlated to the therapeutic success. It is essential to understand the interfering factors in IR to prevent the HSCT-related mortality.

Methods: We retrospectively evaluated the clinical outcomes, absolute lymphocyte counts (ALCs) and lymphocyte subtypes at different time-points of 111 pediatric patients with allogeneic HSCT for malignant and non-malignant diseases from 2013 to 2018.

Results: The ALCs gradually increased on D+30, D+100, and D+180 (medians 634/μL, 1022/μL and 1541/μL, respectively). On D+100, the CD3+CD8+ achieved the highest recovery rate (68%), followed by the CD16+CD56+ (47%), CD3+CD4+ (39%) and CD19+ (8%). The adequate ALC recovery was associated with age < 8 years, bone marrow grafts, myeloablative conditioning, non-use of serotherapy and non-haploidentical donors. The ALC and CD3+CD8+ on D+100 counts were higher in patients with the cytomegalovirus infection. The CD3+CD4+ recovery was associated with an age < 8 years, a non-malignant disease and a lower incidence of acute graft-versus-host disease ≥ grade 2. Furthermore, the ALC recovery on D+100 resulted in a higher overall survival, regardless of the disease type (HR 3.65, 1.05 - 12.71, p = 0.04).

Conclusion: Several factors influenced the IR after the allo-HSCT. The ALC ≥ 500/μL on D+100 was a simple IR predictor of survival, easily available to resource-limited centers.

Keywords: Hematopoietic stem cell transplantation; Immune reconstitution; Lymphocyte count; Lymphocyte subpopulations; Pediatrics.

Figure 1

Patients included in the study. Dotted arrows represent excluded patients. Abbreviations: ALC, absolute lymphocyte count; allo-HSCT, allogenic hematopoietic stem cell transplantation; D+0, day +0; D+30, day +30; D+100, day +100; D+180, day +180.

Figure 2

Lymphocyte reconstitution after hematopoietic stem cell transplantation. A: Absolute lymphocyte counts on D+30, D+100 and D+180 according to the type of donor. Median absolute lymphocyte count on D+30: matched siblings 746/µL, haploidentical 441/µL and unrelated 616/µL, p = 0.03; D+100: matched siblings 1,152/µL, haploidentical 1,066/µL and unrelated 903/µL, p = not significant; D+180: matched siblings 1,714/µL, haploidentical 1,321/µL and unrelated 1,778/µL, p = not significant. The line over bars indicates groups significantly different (Kruskal-Wallis test). For scale reasons, three outlier counts on D+180 are not shown (10,195/µL of matched siblings, 10,404/µL of haploidentical and 14,432/µL of unrelated). B: Lymphocyte subtypes counts on D+100. Red lines represent the medians for each subtype. Dashed line shows the 200/µL cut-off value for CD3+CD4+, CD3+CD8+ and CD19+. The dotted line shows the 150/µL cut-off value for CD16+CD56+. C-F: Reconstitution of lymphocyte subpopulations on D+100 according to the type of donor (n = 74, Kruskal-Wallis test). C: CD3+CD4+ reconstitution. D: CD3+CD8+ reconstitution. E: CD19+ reconstitution. F: CD16+CD56+ reconstitution. Abbreviations: D+30, day+30; D+100, day +100; D+180, day +180; NS, not significant. In boxplot graphs, circles (○) represent outlier values and diamonds (◇) represent far outlier values.

Figure 3

Overall survival according to lymphocyte recovery. A: Overall survival for ALC-recovered patients (blue line) and not recovered (red line) on D+100 (Kaplan-Meier) and its Hazard Ratio by univariate Cox regression. B: Overall survival (Kaplan-Meier) and log-rank of CD3+CD4+-recovered patients (blue line) and not recovered (red line) on D+100. Abbreviations: ALC, absolute lymphocyte count; HR, Hazard ratio.