Liposomal vincristine is designed to reduce neurotoxicity and increase dose 
intensity delivery, and has been approved as salvage therapy in 
relapsed/refractory acute lymphoblastic leukemia (ALL). Our aim was to evaluate 
the response rate, toxicities, and outcome of adults with newly diagnosed ALL 
who received liposomal vincristine, rather than regular vincristine in 
combination with intensive chemotherapy (Hyper-CMAD). In a single-center, phase 
2 study, patients ≥18 years with newly-diagnosed B-cell ALL were eligible to 
receive hyper-CMAD alternating with high-dose methotrexate and cytarabine. 
Rituximab was administered in CD20 positive ALL. Tyrosine kinase inhibitors 
(imatinib or dasatinib) were added in Philadelphia chromosome-positive 
(Ph-positive) ALL. Thirty-one patients were enrolled, median follow-up of 
59 months (0.3-70). Thirteen patients (42%) had CD20 positive ALL, and 21 (68%) 
had Ph-positive ALL. Thirty (97%) achieved complete remission (CR). All 26 
patients with abnormal karyotype achieved complete cytogenetic response (CCyR), 
and 27/30 (90%) achieved negative minimal residual disease status by multicolor 
flow cytometry. Of 20 evaluable Ph-positive ALL patients, major molecular 
response (MMR) was achieved in 19 patients (95%); complete molecular response 
(CMR) in 14 (70%). Grade 3/4 peripheral neuropathy was observed in five (16%) 
with all grade peripheral neuropathy in 21 (68%). With a median follow-up of 
59 months, 21 (68%) patients are alive. The 5-year CR duration and survival 
rates were 73% and 61%, respectively. Ten (32%) patients died: one, sepsis on 
C1D10; four, unknown; one, post-transplant complications; four, relapse. 
Hyper-CMAD with liposomal vincristine is safe and demonstrated high response and 
survival rates in newly diagnosed ALL.