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

• Published in: Leukemia Vol. 32; no. 3; pp. 626 - 632
• Main Authors: Sakura, T, Hayakawa, F, Sugiura, I, Murayama, T, Imai, K, Usui, N, Fujisawa, S, Yamauchi, T, Yujiri, T, Kakihana, K, Ito, Y, Kanamori, H, Ueda, Y, Miyata, Y, Kurokawa, M, Asou, N, Ohnishi, K, Ohtake, S, Kobayashi, Y, Matsuo, K, Kiyoi, H, Miyazaki, Y, Naoe, T
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.03.2018
• Subjects: Acute lymphoblastic leukemia; Acute lymphocytic leukemia; Analysis; Clinical trials; Dosage and administration; Drug therapy; Leukemia; Lymphatic leukemia; Methotrexate; Patient outcomes; Patients; Philadelphia chromosome; Remission; Survival; Therapy; Treatment outcome
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2017.283

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/m ) or Id-MTX (0.5 g/m ). 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.