Pairwise combinations of romidepsin, idasanutlin, and cladribine inhibit leukemic outgrowth in a T-PLL PDX model. (A-B) System of xenografts of leukemic cells from 1 patient with T-PLL (PDXs), investigating the efficacy and toxicity of idasanutlin with cladribine (green), idasanutlin with romidepsin (blue), and cladribine with romidepsin (red) compared with vehicle control–treated mice (orange; n = 4 per condition). (A) Scheme of scheduling and dosing: T-PLL cells from the patient were transduced with the lentivirus expressing firefly luciferase-GFP, sorted to >99% GFP positivity, and transplanted into Rag^−/−γc^−/− mice with 2 million cells. After confirming the engraftment of leukemia cells in vivo after 3 weeks, cohorts of mice were randomly assigned to treatment with vehicle or combinations. The substances were given at the indicated time points and with the presented dosages (p.o., by mouth; i.p., intraperitoneal; b.i.d., twice a day). Mice were imaged weekly using an IVIS imager. Blood smear (upper-right corner) at 3 months after initial engraftment in the vehicle control group, showing the typical prolymphocytic morphology of a T-PLL cell. (B) Luciferase bioluminescence presented as total flux (photons/second [p/s]) over time of mice with T-PLL PDXs, treated with the indicated combinations. Within the graph, representative bioluminescence images for each treatment cohort are presented (d21 = before first cycle; d63 = 6 days after second cycle; d91 = 6 days after third cycle; d124 = 6 days after fourth cycle). All tested combinations significantly decelerated the tumor outgrowth of T-PLL PDXs in mice. See supplemental Figure 10 for RBCs and PLTs before and after treatment cycle 3. IVIS, in vivo imaging system.