MTXPGs and effects on DNPS.

(A,B) MTXPGs were measured in bone marrow aspirates at 44 hours after the start of MTX (n = 106). (A) In patients with hyperdiploid (LDMTX plus MP: n = 9; HDMTX plus MP: n = 13) or nonhyperdiploid B-lineage ALL (LDMTX plus MP: n = 28; HDMTX plus MP: n = 33), total MTXPG concentrations (MTXPG_1-7) were higher in those randomized to HDMTX plus MP compared with LDMTX plus MP (P < .01). In contrast, HDMTX plus MP did not achieve higher MTXPG_1-7 concentrations in patients with T lineage (P = .49). (B) Similar trends were observed with long-chain MTXPG concentrations (MTXPG_4-7). (C,D) Full DNPS inhibition was associated with higher MTXPG_1-7concentrations in ALL blasts compared with partial or no inhibition of DNPS (C). Lower MTXPG_1-7 concentrations were required to achieve DNPS inhibition in patients with T-lineage (n = 14) compared with those with B-lineage ALL (n = 38) (P < .01). (D) Similar trends were observed with long-chain MTXPG_4-7concentrations.