Figure 2
Figure 2. Serial measurement of 2-HG during therapy. Serum (A) and urine (B) 2-HG levels measured serially over the course of the first 60 days of treatment for patients with baseline elevations in 2-HG and who achieved complete remission after induction chemotherapy. (C) IDH1/2-mutant allele burden measured serially in marrow samples over the course of the first 30 days of treatment for 3 of these patients with complete remission after induction chemotherapy. (D-F) Serum (D) and urine (E) 2-HG levels measured serially over time for a patient (patient 1 in panels A-C) who received cytarabine- and idarubicin-based induction, went on to relapse at ∼ day 150, and was then treated with reinduction therapy consisting of mitoxantrone, etoposide, and cytarabine (MEC), to which he responded transiently before displaying refractory disease. (F) IDH1-mutant allele burden for the same patient, measured serially in marrow samples, displaying initial decrease in IDH1-mutant allele burden with remission, with subsequent increase associated with relapse. (G-H) Serum (G) and urine (H) 2-HG levels measured serially over time (∼ 250 days) for a patient who received hypomethylating therapy with 5-azacitidine 75 mg/m2 intravenously on days 1-5 of 28-day cycles.

Serial measurement of 2-HG during therapy. Serum (A) and urine (B) 2-HG levels measured serially over the course of the first 60 days of treatment for patients with baseline elevations in 2-HG and who achieved complete remission after induction chemotherapy. (C) IDH1/2-mutant allele burden measured serially in marrow samples over the course of the first 30 days of treatment for 3 of these patients with complete remission after induction chemotherapy. (D-F) Serum (D) and urine (E) 2-HG levels measured serially over time for a patient (patient 1 in panels A-C) who received cytarabine- and idarubicin-based induction, went on to relapse at ∼ day 150, and was then treated with reinduction therapy consisting of mitoxantrone, etoposide, and cytarabine (MEC), to which he responded transiently before displaying refractory disease. (F) IDH1-mutant allele burden for the same patient, measured serially in marrow samples, displaying initial decrease in IDH1-mutant allele burden with remission, with subsequent increase associated with relapse. (G-H) Serum (G) and urine (H) 2-HG levels measured serially over time (∼ 250 days) for a patient who received hypomethylating therapy with 5-azacitidine 75 mg/m2 intravenously on days 1-5 of 28-day cycles.

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