ORLANDO, FL—Adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) had significantly higher rates of disease-free survival when treated with high-dose—compared to intermediate dose—methotrexate, phase 3 trial results reported at the 57th American Society of Hematology (ASH) Annual Meeting have shown.1

Although randomized controlled trials have confirmed the effectiveness of treatment with high-dose methotrexate in pediatric ALL, similar data have not confirmed use of this regimen in adults, explained Toru Sakura, MD, PhD of the Leukemia Research Center at the Saiseikai Maebashi Hospital in Japan, in describing the rationale for the Japan Adult Leukemia Study Group’s phase 3 randomized trial of high-dose vs intermediate-dose methotrexate therapy adult ALL.

The study enrolled 341 patients between the age of 25 to 64. The 229 patients who achieved a complete remission sustained at the beginning of the third course of therapy were randomly assigned to either high-dose methotrexate (3 g/m2; n=115) or intermediate-dose methotrexate (0.5 g/m2; n=114), both administered on day 1 and 15.

Continue Reading

“The same therapy was repeated on the fifth course,” Dr. Sakura said.

Primary study end point was rate of disease-free survival (DFS); secondary end points were to assess toxicity and rates of complete remission and overall survival.

Results showed the estimated 5-year disease-free survival rate of those who received high-dose methotrexate to be 58% (95% CI: 45–68), “significantly better” than those receiving intermediate-dose methotrexate, 32% (95% CI: 22-43; P = .0218), Dr. Sakura reported.

Patients in the intermediate-dose methotrexate group who relapsed were better rescued by stem cell transplantation, “which would make the difference of overall survival” between the 2 groups smaller.

The frequency of severe adverse events was similar between the 2 groups, Dr. Sakura reported, leading the investigators to conclude that high-dose methotrexate “appeared to be feasible” in the treatment of adult ALL.


1. Sakura T, Hayakawa F, Sugiura I, et al. Effectiveness of high-dose MTX therapy for adult Ph-negative ALL by randomized trial: JALSG ALL202-O. Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting; December 5, 2015, Orlando, FL.