Comparison of the effects of early intensified induction chemotherapy and standard 3+7 chemotherapy in adult patients with acute myeloid leukemia

Abstract

BackgroundStandard remission induction chemotherapy consisting of anthracycline plus cytarabine (3+7) is administered for adult acute myeloid leukemia (AML). However, the effects of intensified regimen on complete remission (CR), relapse and overall survival (OS) remain unknown.MethodsWe analyzed 1195 patients treated with idarubicin plus cytarabine/BHAC (3+7) from 2002 to 2013. Among them, 731 received early intensification with 3-day cytarabine/BHAC (3+10, N=363) or 2-day idarubicin plus cytarabine/BHAC 3 days (5+10, N=368). The 3+10 and 5+10 strategies were applied to patients with bone marrow blast counts of 5–20% and >20% on day 7 of 3+7, respectively.ResultsEarly intensification correlated with a younger age (median: 40 vs. 45 yr) and higher t(8;21) frequency (20.4% vs. 7.1%), compared to 3+7. After early intensification, the early death rates were higher among the elderly (3+10 [15.7%], 5+10 [21.7%] vs. 3+7 [6.3%], P=0.038), while the post-induction CR rate was higher in young patients (3+10 [79.8%], 5+10 [75.1%] vs. 3+7 [65.1%], P<0.001). Early relapse rate was also decreased (3+10 [11.8%], 5+10 [11.7%] vs. 3+7 [22.0%], P<0.001). In multivariate analysis, early intensification correlated with an inferior 5-year OS among elderly patients (19.2% vs. 22.8%; hazard ratio [HR]=1.84, 95% confidence interval [CI]; 1.11–3.06, P=0.018) and lower overall relapse rate among young patients (33.0% vs. 41.4%, P=0.023; HR=0.71, 95% CI; 0.55–0.93, P=0.012).ConclusionEarly intensification correlated with higher CR and lower relapse rates, but not OS in young AML patients. In elderly patients, early intensification correlated with a higher early death rate and poorer OS.

Pin1 inhibition exerts potent activity against acute myeloid leukemia through blocking multiple cancer-driving pathways

“…Chemotherapeutic approaches continue to be the mainstay therapies used for AML treatments [ 13 ]. However, long-term survival using these therapies is only obtained in 35 to 40% of younger patients [ 14 , 15 ], and the long-term survival of elderly AML patients is even lower because only about one third of them are eligible for intensive chemotherapies [ 16 ]. Therefore, therapy still needs to come a long way to fully overcome AML.…”

Specific donor HLA allotypes as predictors of cytomegalovirus disease risk in acute myeloid leukemia

“…As a reduced‐intensity conditioning regimen, we administered 6.4 mg/kg of busulfan (3.2 mg/kg for 2 days) and 150 mg/m 2 of fludarabine (30 mg/m 2 for 5 days) with 400 cGy of total body irradiation. For haploidentical familial mismatched donors, we administered 150 mg/m 2 of fludarabine (30 mg/m 2 for 5 days) and 6.4 mg/kg of busulfan (3.2 mg/kg for 2 days) with 800 cGy of total body irradiation and 1.25 mg/kg of anti‐thymocyte globulin for four consecutive days 6‐8 . Graft vs host disease (GVHD) prophylaxis was administered using a calcineurin inhibitor plus a short course of methotrexate on days 1, 3, 6, and 11.…”

Immunity or morphogenesis in cancer development and treatment

“…Treatment usually continues until it has a chance to work but, in parallel, from cycle to cycle it exhausts regenerative capacity of lymphopoiesis, and induces serious complications, including incurability and a higher risk of death. People who are much older and have exhausted lymphopoiesis may not be able to tolerate intense treatment, which brings no benefit, despite its intensification [88].…”