Varying intensity of postremission therapy in acute myeloid leukemia

Abstract

The Eastern Cooperative Oncology Group (ECOG) conducted a randomized trial in patients less than or equal to 65 years old (median, 44 years) to determine whether increasing the intensity of postremission therapy in acute myeloid leukemia (AML) would improve the outcome. After uniform induction therapy, patients in complete remission (CR) who were less than 41 years old and who had a histocompatible sibling underwent allogeneic bone marrow transplantation (alloBMT) (54 patients). The remainder of patients in CR were randomized to receive either 2 years of continuous outpatient maintenance therapy with cytarabine and 6- thioguanine (83 patients) or a single course of inpatient consolidation therapy consisting of 6 days of high-dose cytarabine plus 3 days of amsacrine (87 patients). The median duration of follow-up is now 4 years, and patients are included in the analyses of outcome regardless of whether they relapsed before starting the intended treatment. Four- year event-free survival (EFS) was 27% +/- 10% for consolidation therapy versus 16% +/- 8% for maintenance therapy (P = .068) and 28% +/- 11% versus 15% +/- 9% (P = .047) in patients less than 60 years old. The outcome for patients receiving alloBMT was compared with the subset of patients less than 41 years old who received consolidation therapy (N = 29) or maintenance therapy (N = 21). Four-year EFS was 42% +/- 13% for alloBMT, 30% +/- 17% for consolidation therapy, and 14% +/- 15% for maintenance therapy. AlloBMT had a significantly better EFS (P = .013) than maintenance therapy, but was not different from consolidation therapy. In patients less than 41 years old, 4-year survival after alloBMT (42% +/- 14%) did not differ from consolidation therapy (43% +/- 18%), but both were significantly better than maintenance therapy (19% +/- 17%), P = .047 and .043, respectively. The mortality rate for maintenance therapy was 0%, consolidation therapy, 21%; and alloBMT, 36%. Consolidation therapy caused an especially high mortality rate in the patients greater than or equal to 60 years old (8 of 14 or 57%). The toxicity of combined high-dose cytarabine and amsacrine is unacceptable, especially in older patients, and alternative approaches to consolidation therapy such as high-dose cytarabine alone need to be tested. In AML, a single course of consolidation therapy or alloBMT after initial CR produces better results than lengthy maintenance therapy. Although EFS and survival of alloBMT and consolidation therapy do not differ significantly, a larger number of patients need to be studied before concluding that they are equivalent.

Impact of postremission consolidation chemotherapy on outcome after reduced‐intensity conditioning allogeneic stem cell transplantation for patients with acute myeloid leukemia in first complete remission: A report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

“…The role of consolidation chemotherapy after successful remission induction is well established in the treatment paradigm of patients with acute myeloid leukemia (AML) in first complete remission (CR1) in the nontransplant setting. [1][2][3] Consolidation chemotherapy courses have been proven to decrease leukemia recurrence and improve survival. Thus, most contemporary treatment protocols for young patients with AML in CR1 who are not undergoing transplantation include repetitive cycles of highdose cytarabine.…”

“…Thus, most contemporary treatment protocols for young patients with AML in CR1 who are not undergoing transplantation include repetitive cycles of highdose cytarabine. [1][2][3][4] Allogeneic stem cell transplantation (alloSCT) is a potentially curative therapy for patients with AML that likely provides the most potent antileukemic effect of any postremission strategy. 5 Nevertheless, whether there is a need for postremission consolidation chemotherapy before alloSCT is an unresolved issue.…”

MDR 1 expression is an independent prognostic factor for response and survival in de novo acute myeloid leukaemia

“…Treatment of acute myeloid leukaemia (AML) with cytosinearabinoside (Ara-C) and daunorubicin results in approximately 65% complete remission in adults (Yates et al, 1982;Cassileth et al, 1992;Mayer et al, 1994;Rees et al, 1986). However, with conventional post-remission chemotherapy, only 25% of these patients remain relapse-free (Yates et al, 1982;Buchner et al, 1985;Vogler et al, 1984).…”

Update on Optimal Management of Acute Myeloid Leukemia

“…59 Subsequently, the final analysis of the EST 3483 trial revealed that a single course of consolidation or allogeneic transplantation (patients age < 40) were superior to 2 years of maintenance therapy for AML in first remission, and that consolidation with high dose cytarabine (3 gm/m 2 IV over 1 hour every 12 hours for 12 consecutive doses, days 1–6) and amsacrine (100 mg/m 2 /d IV for 3 days, days 7–9) was extremely toxic for patients aged ≥ 60 years (early mortality of 57% for age ≥ 60 vs. 13% for <60 years old). 60 Consolidation regimens have included intensive chemotherapy, non-intensive regimens, allogeneic and autologous transplantation. The choice of consolidation therapy is guided by baseline cytogenetic and molecular markers, with allogeneic transplantation in first complete remission being potentially curative for the unfavorable cytogenetic/molecular subgroup.…”