Blinatumomab is an efficacious and well-tolerated treatment in patients with MRD-positive B-lineage ALL after intensive chemotherapy. T cells engaged by blinatumomab seem capable of eradicating chemotherapy-resistant tumor cells that otherwise cause clinical relapse.

The best strategy for incorporating imatinib in front-line treatment of Ph ؉ acute lymphoblastic leukemia (ALL) has not been established. We enrolled 92 patients with newly diagnosed Ph ؉ ALL in a prospective, multicenter study to investigate sequentially 2 treatment schedules with imatinib administered concurrent to or alternating with a uniform induction and consolidation regimen. Coadministration of imatinib and induction cycle 2 (INDII) resulted in a complete remission (CR) rate of 95% and polymerase chain reaction (PCR) negativity for BCR-ABL in 52% of patients, compared with 19% in patients in the alternating treatment cohort (P ‫؍‬ .01). Remarkably, patients with and without a CR after induction cycle 1 (INDI) had similar hematologic and molecular responses after concurrent imatinib and INDII. In the concurrent cohort, grades III and IV cytopenias and transient hepatotoxicity necessitated interruption of induction in 87% and 53% of patients, respectively; however, duration of induction was not prolonged when compared with patients receiving chemotherapy alone. No imatinib-related severe hematologic or nonhematologic toxicities were noted with the alternating schedule. In each cohort, 77% of patients underwent allogeneic stem cell transplantation (SCT) in first CR (CR1). Both schedules of imatinib have acceptable toxicity and facilitate SCT in CR1 in the majority of patients, but concurrent administration of imatinib and chemotherapy has greater antileukemic

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BACKGROUNDValproic acid (VPA) inhibits histone deacetylase activity and, synergizing with all‐trans retinoic acid (ATRA), achieves differentiation induction of myeloid blast cells in vitro.METHODSWe used VPA in 58 patients with acute myeloid leukemia (AML) who were too old and/or medically unfit to receive intensive chemotherapy (32 AML secondary to myelodysplastic syndrome [MDS], 22 de novo AML, 4 AML secondary to myeloproliferative syndrome). VPA serum concentrations were 50–100 μg/mL. Thirty‐one patients received VPA monotherapy. ATRA was added later in 13 patients who did not respond or who relapsed. Another 27 patients received VPA plus ATRA from the start. Median treatment duration was 93 days for VPA and 88 days for ATRA.RESULTSThe response rate was only 5% according to International Working Group (IWG) criteria for AML but was 16% when IWG response criteria for MDS were used, which capture hematologic improvement and stabilization of the disease. These endpoints, which are not necessarily correlated with diminishing blast counts, are relevant for the patients' quality of life. Among 23 patients with a peripheral blast count > 5%, 6 (26%) showed a diminishing blast count, and 5 of these had a complete peripheral blast clearance.CONCLUSIONSFuture trials should combine VPA with chemotherapy or demethylating agents. Cancer 2006. © 2005 American Cancer Society.