Lymphocyte subset at time of Epstein‐Barr viremia post‐allogeneic hematopoietic stem cell transplantation in children may predict development of post‐transplant lymphoproliferative disease: CD8:CD20 ratio as a sensitive predictor

Abstract

EBV–associated PTLD following allogeneic HSCT is a serious complication associated with significant mortality. In this retrospective study, we evaluated whether lymphocyte subset numbers and CD8:CD20 ratio at time of EBV viremia in children undergoing allogeneic HSCT could predict development of PTLD. Absolute lymphocyte count, lymphocyte subsets, and CD8:CD20 ratio at the time of EBV viremia were analyzed. Patients who were treated preemptively with rituximab for high blood EBV viral load were excluded. Out of 266 patients transplanted during the study period, 26 patients were included in the analysis. Patients were divided into two cohorts; cohort 1 included patients with EBV‐associated PTLD (n = 5; four with proven, one with probable PTLD). Cohort 2 included patients with EBV viremia without PTLD (n = 21). Lymphocyte recovery was slower in the PTLD group. CD8:CD20 ratio was significantly lower in the PTLD group (median 0.15) compared to the non‐PTLD group (median 2.4, P = .012). Using the ROC curve and 1 as the cutoff value, CD8:CD20 ratios were analyzed. In the PTLD group, 4/5 patients (80%) had a ratio <1 whereas in the non‐PTLD group, all 21 patients had a ratio >1. Sensitivity and specificity were 80% and 100%, respectively. Negative and PPVs were 95% and 100%, respectively. Profoundly low T‐cell count and CD8:CD20 ratio may be used to predict development of PTLD in the context of EBV viremia in children post‐allogeneic HSCT. Further studies are needed to validate this finding.

Epstein–Barr Virus Monitoring after an Allogeneic Hematopoietic Stem Cell Transplant: Review of the Recent Data and Current Practices in Canada

“…Of note, PTLD subtypes are inconsistently reported and mostly not within the frame of the most recent WHO classification. Across studies, there is again a wide variability in the reported incidence, ranging from as low as 0% to 3.5% in children [4,[8][9][10][11] and 0% to 14% in adults [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31], falling within the range of previously reported incidences. Again, this variability most likely results from the heterogeneity of the transplant populations studied, GvHD prophylaxis, including the use of ATG or not, conditioning regimen administered, as well as donor EBV status.…”

“…The results of EBV reactivation after HSCT in both adults and children are shown in Table 1. Incidence remains highly variable, ranging from 30% to 68% in children [4,[8][9][10][11] and 19% to 86% in adults [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] (excluding Marinho-Diaz et al, 2018, with an unrepresentative six adults studied). This variability reflects a high level of heterogeneity in the reported patient populations, including conditioning regimens, GvHD prophylaxis, donor type, or sensitivity of diagnostic tests.…”

Factors Associated with Post-Transplant Active Epstein-Barr Virus Infection and Lymphoproliferative Disease in Hematopoietic Stem Cell Transplant Recipients: A Systematic Review and Meta-Analysis

“…In total, 3362 titles were identified in the research bases, 1883 in EMBASE and 1479 in Medline. Once duplicates and papers with exclusion criteria were removed, 77 articles [ 4 , 16 , 23 , 24 , 27 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ,…”

“…The method used to diagnose PTLD was not detailed in one study. The length of follow-up was an important source of variation between studies; in some cases the follow-up period was not reported [ 31 , 32 , 34 , 40 , 46 , 48 , 52 , 55 , 59 , 61 , 63 , 73 , 81 , 83 , 86 , 90 , 94 , 98 , 100 ].…”

“…For the same risk factors explored in both studies, those from Kalra et al [67] were retained as the analyses were done on a larger sample. In addition, the Ali et al [31] and Althubaiti et al [32] studies were carried out with non-disjoint samples, but both were retained because different variables were explored. The reasons for exclusion of these articles were as follows: Two articles were excluded because their sample is a subset of the sample from two other articles.…”