Journal Article

High-dose methotrexate therapy significantly improved survival of adult acute lymphoblastic leukemia: a phase III study by JALSG

Ueda, Y, Naoe, T, Sugiura, I, Yujiri, T, Kakihana, K, Imai, K, Ito, Y, Asou, N, Murayama, T, Kanamori, H, Yamauchi, T, Miyata, Y, Fujisawa, S, Kobayashi, Y, Sakura, T, Matsuo, K, Kiyoi, H, Kurokawa, M, Usui, N, Hayakawa, F, Ohnishi, K, Miyazaki, Y, Ohtake, S

2018

Overview

High-dose methotrexate (Hd-MTX) therapy has recently been applied to the treatment of adult acute lymphoblastic leukemia (ALL) based on pediatric protocols; however, its effectiveness for adult ALL has not yet been confirmed in a rigorous manner. We herein conducted a randomized phase III trial comparing Hd-MTX therapy with intermediate-dose (Id)-MTX therapy. This study was registered at UMIN-CTR (ID: C000000063). Philadelphia chromosome (Ph)-negative ALL patients aged between 25 and 64 years of age were enrolled. Patients who achieved complete remission (CR) were randomly assigned to receive therapy containing Hd-MTX (3 g/m2 ) or Id-MTX (0.5 g/m2 ). A total of 360 patients were enrolled. The CR rate was 86%. A total of 115 and 114 patients were assigned to the Hd-MTX and Id-MTX groups, respectively. The estimated 5-year disease-free survival rate of the Hd-MTX group was 58%, which was significantly better than that of the Id-MTX group at 32% (P=0.0218). The frequencies of severe adverse events were not significantly different. We herein demonstrated the effectiveness and safety of Hd-MTX therapy for adult Ph-negative ALL. Our results provide a strong rationale for protocols containing Hd-MTX therapy being applied to the treatment of adult ALL.

• Publisher: Nature Publishing Group
• Subject: Acute lymphoblastic leukemia / Immunomodulators / Leukemia / Lymphatic leukemia / Methotrexate / Patients / Philadelphia chromosome / Remission / Survival / Therapy