Early peripheral blood blast clearance during induction chemotherapy for acute myeloid leukemia predicts superior relapse-free survival.

In childhood acute lymphoblastic leukemia (ALL), a rapid decline of circulating leukemic blasts in response to induction chemotherapy or prednisone is one of the most important prognostic factors, not only for achieving remission but also for relapse-free survival (RFS). However, in acute myeloid leukemia (AML) parameters of chemosensitivity have been restricted mainly to the rapidity of achievement of complete remission (CR) or the assessment of residual leukemic bone marrow blasts during aplasia. We hypothesized that the time to circulating peripheral blood blast clearance, as a potential surrogate for in vivo chemosensitivity, would have prognostic relevance in AML also. In a retrospective analysis of a cohort of 86 adult patients with AML receiving uniform induction and consolidation chemotherapy, we demonstrate that the time to clearance of circulating blasts during induction chemotherapy is an independent prognostic marker of RFS, superseding other known or established risk factors, including karyotype and number of inductions to achieve CR.

Thromboembolism in adults with acute lymphoblastic leukemia during induction with L-asparaginase-containing multi-agent regimens: incidence, risk factors, and possible role of antithrombin.

Thromboembolism (TE) is a known complication of L-asparaginase (ASP) therapy of acute lymphoblastic leukemia (ALL), possibly attributable to reduced synthesis of natural anticoagulants, in particular antithrombin (AT). This retrospective single institution study was performed to determine the TE incidence among adults undergoing induction with contemporary, ASP-containing regimens. Ten of 54 (18.5%) consecutive adults developed symptomatic, objectively confirmed TE, at a median of 5.5 days after the first ASP dose. These were notable for CNS and upper extremity localization, varied significantly according to ALL immunophenotype (precursor B: 11% vs. T cell: 33%), without apparent effect of schedule or total dose of ASP. Median baseline AT level was 94% and fell to a nadir of 47% (P < 0.0001) during ASP therapy. Prophylactic AT had been given to 17 during ASP therapy. None of these developed TE vs. 10/37 (27%) without replacement (P = 0.021). These observations merit further study to gain insight into disease and/or therapy-specific pathogenesis of TE in this population and call for the prospective evaluation of appropriate prophylactic interventions.