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One important prognostic indicator in pediatric leukemia is minimal residual disease (MRD) detected at the end of induction chemotherapy. Detecting any level of MRD in the bone marrow (BM) at the end of induction (MRD+) is associated with increased risk of relapse and poorer overall survival compared to having no MRD detected (MRD-). Discovering differences between these patients, specifically in T cell subsets such as memory T cells and T memory stem cells (Tscm), could lead to new targets for cancer therapy and improvement in treatment for higher risk disease.
To determine potential differences in the frequency of T cell populations in human leukemia in patients with MRD+ versus MRD- disease after induction chemotherapy.
Samples were from 8 patients with premature B cell acute lymphoblastic leukemia (pre-B ALL) from BM. Timepoints were diagnosis and day 29 (D29) of induction chemotherapy. 4 patients were MRD+ after induction and 4 patients were MRD-. Flow cytometric analysis of cytotoxic memory T cell populations was performed and analyzed using descriptive statistics and the t-test.
For all patients, both MRD+ and MRD-, the mean live cell percentages were not different between diagnosis and D29 (76.9% vs 85.1%, p=0.111). CD3+, CD4+, and CD8+ T cells were all higher at D29 (CD3+- 2.1% vs 6.5%, p=0.011; CD4+- 1.0% vs 2.7%, p=0.044; CD8+-0.8% vs 2.7%, p=0.018). Naïve T cells increased from diagnosis to D29 (0.4% vs 3.4%, p=0.009). Tscm were also elevated at D29 (0.01% vs 0.08%, p=0.042). When the patients were subgrouped based on MRD status, similar differences were seen in the MRD- group between diagnosis and D29 (CD3+- 2.2% vs 7.8%, p=0.039; CD4+- 0.8% vs 4.0%, p=0.035; CD8+- 1.1% vs 3.3%, p=0.073; Naïve- 0.4% vs 3.8%, p=0.039; Tscm- 0.02% vs 0.1%, p=0.037). In the MRD+ subgroup, none of the previously described differences were detected (CD3+- 2.0% vs 5.1%, p=0.197; CD4+- 1.1% vs 1.4%, p=0.644; CD8+- 0.6% vs 2.17%, p=0.175; Naïve- 0.5% vs 2.95%, p=0.173; Tscm- .004% vs 0.02%, p=0.355).
Recovery of immune function is anticipated after induction chemotherapy for pre-B ALL. Our data demonstrate the expected increase in T cell subsets in patients with MRD- BM at D29 but not in patients with MRD+ BM. The discovery of poorer immunological recovery in MRD+ patients requires additional study to determine what makes MRD+ disease different. This could introduce new immunotherapy targets in human leukemia.
McElroy, Sara; Tao, Fang; Szarejko, John; and Perry, John M., "T Cell Populations And Response To Chemotherapy In Human Leukemia" (2022). Research at Children's Mercy Month 2022. 21.