Augmented Hyper-CVAD in Acute Lymphoblastic Leukemia (ALL): The MDACC Experience with Intensified L-Asparaginase and Vincristine in Adult ALL Salvage.

Prognosis has improved in newly diagnosed adult ALL using dose-intense multiagent regimens. Outcome of 185 patients (pts) treated with Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) showed 91% CR rate with 5-yr. survival of 39% and low induction mortality (Kantarjian et al. JCO 18:547, 2000). Outcome remains poor in ALL salvage. Following leads in pediatric ALL, we hypothesized that “augmentation” of hyper-CVAD (AHCVAD) with vincristine, dexamethasone, and L-asparaginase during induction and consolidation may improve prognosis in adult ALL salvage. To evaluate efficacy and safety of AHCVAD we conducted a phase II study, in which pts received up to 8 courses of HCVAD alternating with methotrexate/high-dose cytarabine. Each course was augmented by L-asparaginase 20,000 units i.v. and vincristine 2 mg i.v. at days 1, 8, and 15 each, and dexamethasone 80 mg i.v./p.o. on days 1–4 and 15–18. From June 2003 to June 2005, 29 pts with relapsed/refractory ALL were treated. Median age was 32 yrs (range 14–70). Twenty-two pts (76%) had pre-B ALL (1 isolated CNS disease), 6 (21%) T cell ALL (2 with isolated extramedullary disease), and 1 (3%) pt had mature B ALL. Karyotype was diploid in 11 (44%) and abnormal in 14 (56%) pts (1 Ph+ ALL). No information is available in 4 pts. Median number of prior regimens was 1 (1–4). Median remission duration to initial induction regimen was 9 mos (0–68). Three pts were primary refractory. Of 29 pts, 22 are evaluable for response (2 too early, 5 off study for toxicity or pt. choice). Eight pts (37%) achieved CR, 1 (5%) PR, and 2 (10%) hematologic improvement (HI) for an OR of 52%. Six pts were able to proceed with stem cell transplant (5 CR, 1 HI). Of 29 pts evaluable for toxicity, 5 (17%) died on study from infectious complications. Uncomplicated neutropenic fever was common. Three pts (10%) were intolerant to L-asparaginase and had to be taken off study early. In summary, AHCVAD has activity in ALL salvage. However, asparaginase-related toxicities and neutropenic complications remain frequent and may limit the usefulness of this approach to selected patient populations.