Absolute lymphocyte counts at end of induction correlate with distinct immune cell compartments in pediatric B cell precursor acute lymphoblastic leukemia

Abstract

Several retrospective studies in children with B cell precursor (BCP) acute lymphoblastic leukemia (ALL) provided clinical evidence that higher absolute lymphocyte counts (ALC) early into treatment significantly correlated with improved relapse-free and overall survival. It still remains unknown, however, whether the predictive role of higher ALCs reflects general bone marrow recovery or a more specific attribute of immune function. To investigate this question, we implemented a prospective observational cohort study in 20 children with BCP ALL on day 29 (D29) of induction chemotherapy and immunophenotyped their lymphoid (T, B and natural killer cells) and myeloid (neutrophils, monocytes, dendritic cells) compartments. In a first evaluation of a cohort treated with Children's Oncology Group-based induction chemotherapy, the immune cell compartments were differentially depleted at D29. Neither gender, risk status, minimal residual disease, nor bone marrow recovery markers correlated with D29 ALC. In contrast, both CD3 T cell and dendritic cell compartments, which did not correlate with age, significantly correlated with D29 ALC (p < 0.0001). In addition, subset complexity of cellular immune compartments was preserved at D29. This study reveals that D29 ALC significantly correlates with distinct immune cell compartments but not with bone marrow recovery markers, suggesting that higher D29 ALCs may contribute to leukemia control by inducing specific host immune activity.

Prognostic Significance of Absolute Lymphocytic Count Recovery in Pediatric Patients with Acute Lymphoblastic Leukemia at South Egypt Cancer Institute

“…The median WBC at diagnosis was 17.2 × 10 3 cell/ ul which considered high when compared to 9.22 × 10 3 cells/ul reported by Farkas et al [1] and 12.260 cell/ul by Hatzipantelis et al [12] which may be explained by a higher incidence of T phenotype among our patients. This comes true when we found that the median initial WBC count of 4300 cell/ul reported by Rolf et al [19] who studied ALC in a group of patients with B-ALL. and evaluated their impact as a prognostic factor in ALL at two different cut off levels ALC 350 (< or ≥350 cell/µl) and ALC 500 (< or ≥500 cell/µl).…”

“…Farkas et al [1] and Gupta et al [2] reported that their patients with low ALC values tend to have a higher risk (MR or HR groups) and a higher age at diagnosis (>10 years) on day 15 of induction with similar cutoff ALC value. Rolf et al [19] when investigated the relationship between D29 ALC and age as continuous variables also reported a significant inverse correlation (r = −0.47; p = 0.033). A finding that confirms the general observation that lymphocyte counts decrease with increasing age [20].…”

Differential Depletion of Bone Marrow Resident B-ALL after Systemic Administration of Endosomal TLR Agonists

“…The absolute lymphocyte count (ALC) at the end of induction therapy is also reported to be a strong prognostic indicator in pediatric ALL; patients with high ALC are at significantly reduced risk of recurrence [8][9][10][11][12]. While the biology underlying this association remains unclear, we observed that the ALC was not simply a reflection of bone marrow recovery [13]; numbers of specific immune cell subsets, including T cells and dendritic cells, were most strongly correlated with ALC, suggesting a potential role for the endogenous immune system in the prevention of recurrence. Stimulation of this immune environment during early treatment could contribute to greater immune control of ALL progression.…”

“…Furthermore, the significant increase in the number of cDCs following CpG ODN treatment may represent the accumulation of mature DCs with migratory capacity capable of priming T cells required for establishing long-term protection against ALL. Notably, the cell populations implicated in the TLR-induced control of primary B-ALL in this study are present early in treatment at numbers that correlate with ALC [13].…”