TY - JOUR
T1 - Immune composition and its association with hematologic recovery after chemotherapeutic injury in acute myeloid leukemia
AU - Kenswil, Keane Jared Guillaume
AU - Pisterzi, Paola
AU - Feyen, Jacqueline
AU - ter Borg, Mariëtte
AU - Rombouts, Elwin
AU - Braakman, Eric
AU - Raaijmakers, Marc Hermanus Gerardus Petrus
N1 - Publisher Copyright: © 2021 ISEH – Society for Hematology and Stem Cells
PY - 2022/1
Y1 - 2022/1
N2 - Chemotherapy-induced bone marrow (BM) injury is a significant cause of morbidity and mortality in acute myeloid leukemia (AML). Time to hematologic recovery after standard (“7 + 3”) myeloablative chemotherapy can vary considerably among patients, but the factors that drive or predict BM recovery remain incompletely understood. Here, we assessed the composition of innate and adaptive immune subsets in the regenerating BM (day 17) after induction chemotherapy and related it to hematologic recovery in AML. T cells, and in particular the CD4 central memory (CD4CM) T-cell subset, were significantly enriched in the BM after chemotherapy, suggesting the relative chemoresistance of cells providing long-term memory for systemic pathogens. In contrast, B cells and other hematopoietic subsets were depleted. Higher frequencies of the CD4CM T-cell subset were associated with delayed hematopoietic recovery, whereas a high frequency of natural killer (NK) cells was related to faster recovery of neutrophil counts. The NK/CD4CM ratio in the BM after chemotherapy was significantly associated with the time to subsequent neutrophil recovery (Spearman's ρ = –0.723, p < 0.001, false discovery rate <0.01). The data provide novel insights into adaptive immune cell recovery after injury and identify the NK/CD4CM index as a putative predictor of hematopoietic recovery in AML.
AB - Chemotherapy-induced bone marrow (BM) injury is a significant cause of morbidity and mortality in acute myeloid leukemia (AML). Time to hematologic recovery after standard (“7 + 3”) myeloablative chemotherapy can vary considerably among patients, but the factors that drive or predict BM recovery remain incompletely understood. Here, we assessed the composition of innate and adaptive immune subsets in the regenerating BM (day 17) after induction chemotherapy and related it to hematologic recovery in AML. T cells, and in particular the CD4 central memory (CD4CM) T-cell subset, were significantly enriched in the BM after chemotherapy, suggesting the relative chemoresistance of cells providing long-term memory for systemic pathogens. In contrast, B cells and other hematopoietic subsets were depleted. Higher frequencies of the CD4CM T-cell subset were associated with delayed hematopoietic recovery, whereas a high frequency of natural killer (NK) cells was related to faster recovery of neutrophil counts. The NK/CD4CM ratio in the BM after chemotherapy was significantly associated with the time to subsequent neutrophil recovery (Spearman's ρ = –0.723, p < 0.001, false discovery rate <0.01). The data provide novel insights into adaptive immune cell recovery after injury and identify the NK/CD4CM index as a putative predictor of hematopoietic recovery in AML.
UR - http://www.scopus.com/inward/record.url?scp=85120854019&partnerID=8YFLogxK
U2 - 10.1016/j.exphem.2021.11.003
DO - 10.1016/j.exphem.2021.11.003
M3 - Article
C2 - 34800603
AN - SCOPUS:85120854019
SN - 0301-472X
VL - 105
SP - 32-38.e2
JO - Experimental Hematology
JF - Experimental Hematology
ER -
