The synergistic combination cladribine/idasanutlin decreases T-PLL burden in MTCP1 transgenic mice, without showing hematologic toxicity. System of syngeneic transplants of leukemic cells from the CD2-hMTCP1^p13 transgenic murine T-PLL model,²⁸ investigating the efficacy as well toxicity of idasanutlin (n = 6), cladribine (n = 5), idasanutlin with cladribine (n = 4), idasanutlin with venetoclax (n = 5), idasanutlin with romidepson (n = 4), and venetoclax with romidepsin (n = 4) compared with vehicle control–treated mice (n = 6). (A) Scheme of scheduling and dosing: mice were injected intraperitoneal (i.p.) with 0.25 × 10⁷ leukemic cells derived from the CD2-hMTCP1^p13 transgenic murine T-PLL–like model. Treatment was performed on days 7 to 11 after transplantation at indicated dosages (p.o., per oral). Blood sampling was performed on day 6 and day 13. Mice were euthanized on day 14. (B) Flow cytometry analysis of CD3 and CD5 expression at day 13 after transplantation, gated on lymphocytes in PB. The T-cell population was significantly reduced after treatment with idasanutlin and cladribine (95% in the vehicle control condition vs 52% in the idasanutlin + cladribine condition). (C-F) Box plots presenting the WBC counts (C), spleen weights (D), red blood cell counts (RBCs) (E), and platelet counts (PLTs) (F). The WBCs, RBCs, and PLTs were calculated on day 13 after transplantation from PB, and the spleen weight was measured on day 14 (mean with SEM; 1-way ANOVA; Bonferroni correction for multiple comparisons, ∗P < .05; ∗∗∗P < .001). See supplemental Figure 9 for proportions of T cells in the bone marrow and relative weight loss upon treatment.