Hyper-CVAD Plus Nelarabine: A Pilot Study for Patients with Newly Diagnosed T Cell Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LL)

Despite improvement in the prognosis of patients (pts) with T-ALL/LL relapses remain frequent and prognosis of relapsed patients is poor. New drugs specific for T-cell lymphoproliferative disorders and treatment programs combining successful strategies of the past with new agents remain critical. Nelarabine is the water-soluble prodrug of the deoxyguanosine analogue guanosine arabinoside (ara-G) and has activity in pts with relapsed/refractory T cell hematologic malignancies. Here we combine hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine for a total of 8 courses, Kantarjian et al. JCO 18:547, 2000) with nelarabine to try and improve response duration and survival of patients with T-ALL/LL. Nelarabine was given at 650 mg/m² i.v. daily × 5 days q 28 days for two courses following completion of the hyper-CVAD sequence and prior to the POMP maintenance (vincristine, prednisone, 6-mercaptopurin, methotrexate). CNS prophylaxis consisted of 8 intrathecal (IT) treatments (2 with each of the first 4 cycles of hyper-CVAD, but not concomitant with nelarabine) alternating IT methotrexate with IT cytarabine. Starting in August 2007, 7 pts with pre-T ALL/LL have been enrolled. Three pts were in CR at study start following prior therapy with hyper-CVAD for a maximum of 3 cycles. Median age was 38 yrs (range 21–76). All pts had a pre-T immunophenotype. One pt had nodal-based disease only, 6 pts had marrow involvement and 4 pts presented with mediastinal masses. No patient had CNS involvement. Cytogenetics were diploid in 6 pts and abnormal in 1 [translocation t(1;14), del(13)]. All patients achieved or maintained a complete remission. Three patients completed the nelarabine consolidations (too early for the remaining pts). The dose of nelarabine had to be reduced to 650 mg/m² on alternate days (1,3, 5) in one pt because of grade 2 toxicity from previous vincristine. No exacerbation of neurotoxicity was noted in any of the patients following nelarabine. The study continues to accrue. Hyper-CVAD achieves a high CR rate in T-ALL/LL. Administration of nelarabine is feasible following the hyper-CVAD induction. Assessment of impact of the nelarabine consolidation on DFS and survival requires higher patient numbers and longer follow up.