J Korean Med Sci.  2015 Oct;30(10):1416-1422. 10.3346/jkms.2015.30.10.1416.

Oral Maintenance Chemotherapy with 6-Mercaptopurine and Methotrexate in Patients with Acute Myeloid Leukemia Ineligible for Transplantation

• Choi YW
• Jeong SH
• Ahn MS
• Lee HW
• Kang SY
• Choi JH
• Park JS

• KMID: 2344173
• DOI: http://doi.org/10.3346/jkms.2015.30.10.1416

Abstract

For decades, maintenance chemotherapy has failed to improve the cure rate or prolong the survival of patients with acute myeloid leukemia (AML), other than those with acute promyelocytic leukemia. Immediately after the first complete remission following consolidation therapy was obtained, oral maintenance chemotherapy (daily 6-mercaptopurine and weekly methotrexate) was given and continued for two years in transplant-ineligible AML patients. Leukemia-free survival (LFS) and overall survival (OS) were studied and compared between these patients and the historical control group who did not receive maintenance therapy. Consecutive 52 transplant-ineligible AML patients were analyzed. Among these patients, 27 received oral maintenance chemotherapy. No significant difference was found in the patients' characteristics between the maintenance and the control groups. The median OS was 43 (95% CI, 19-67) and 19 (95% CI, 8-30) months in the maintenance and the control groups, respectively (P = 0.202). In the multivariate analysis, the presence of maintenance therapy was an independent prognostic factor for better OS (P = 0.021) and LFS (P = 0.024). Clinical benefit from maintenance chemotherapy was remarkable in older patients (> or = 60 yr) (P = 0.035), those with intermediate or unfavorable cytogenetics (P = 0.006), those with initial low blast count in peripheral blood (P = 0.044), and those receiving less than two cycles of consolidation therapy (P = 0.017). Maintenance oral chemotherapy as a post-remission therapy can prolong the survival of patients with AML who are not eligible for transplantation, particularly older patients, those with intermediate or unfavorable cytogenetics, those with initial low blast count, and those receiving less than two cycles of consolidation therapy.

Keyword

Maintenance; Leukemia; Myeloid; Acute

MeSH Terms

6-Mercaptopurine/*therapeutic use
Adolescent
Adult
Aged
Antimetabolites, Antineoplastic/*therapeutic use
Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
Cytarabine/therapeutic use
Disease-Free Survival
Female
Humans
Idarubicin/therapeutic use
Leukemia, Myeloid, Acute/*drug therapy/mortality
Maintenance Chemotherapy/*methods
Male
Methotrexate/*therapeutic use
Middle Aged
Remission Induction
Treatment Outcome
Young Adult
6-Mercaptopurine
Antimetabolites, Antineoplastic
Cytarabine
Idarubicin
Methotrexate

Figure

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  Fig. 1 Survival by the presence or absence of maintenance therapy. (A) Overall survival (OS). (B) Leukemia-free survival (LFS).

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  Fig. 2 Overall survival (OS) of patients with risks by the presence or absence of maintenance therapy. (A) OS of those with intermediate or unfavorable cytogenetics, (B) older patients, (C) those with initial low blast count in peripheral blood, (D) those receiving less than two cycles of consolidation therapy.

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