(A) NOD/SCID mice were injected i.v. with 2.0 pmol/kg CD19L-sTRAIL in a 100 μl volume. Depicted is the plasma concentration/time curve with the estimated PK parameters (n = 16 at 4 hours, n = 16 at 24 hours, n = 12 at 48 hours). The PK parameters were calculated as detailed in Supplemental Methods. (B–D) NOD/SCID mice (5/group) were inoculated with 2 × 10⁶ xenograft cells derived from a relapsed BPL patient. CD19L-sTRAIL was administered i.v. on days 1 and 2 (17 fmol/kg/d). One group received 2 Gy TBI on day 2. The experiment was terminated by euthanasia of all mice in all treatment groups when untreated control mice showed signs of morbidity. Depicted are the mean ± SEM values (n = 5 for control, TBI as well as CD19L-sTRAIL; n = 4 for nonleukemic control NOD/SCID mice) for the spleen size (B), nucleated spleen cell count (C), and absolute lymphocyte count (ALC) (D). Student’s t tests (unequal variances) were performed to compare the control/TBI groups with other groups. *P = 0.0002 vs. CON, ^†P = 0.003 vs. TBI in B; *P < 0.0001 vs. CON or TBI in C; *P = 0.0012 vs. CON, ^†P = 0.0166 vs. TBI, **P = 0.0014 vs. CON in D. (E and F) EFS curves of NOD/SCID mice that were inoculated i.v. with cells from xenograft clone no. 7 and xenograft clone no. 11 (2 × 10⁶ cells/mouse). For E, 11 control mice challenged with xenograft clone no. 7 were left untreated. For F, among the 19 control mice, 14 challenged with xenograft clone no. 11 were left untreated and 5 received 2 Gy TBI on day 2. Treatment protocols with CD19L-sTRAIL and standard chemotherapy are detailed in Supplemental Methods.*P <0.0001 vs. CON, ^†P = 0.0002 vs. chemotherapy in E; *P < 0.0001 vs. CON and TBI in F. P values were calculated utilizing the log-rank test.