Treatment of Elderly and Relapsed/Refractory AML Patient Using Cytosar and Arsenic Trioxide

Introduction:

Treatment of elderly patients with AML and those with relapsed / refractory AML still remains a major challenge. This study was designed and accomplished respecting the lack of a standard treatment and socioeconomic condition in Iran, which make most of the patients unable to afford the related drugs (hypomethylating agents) and some experiences in using Arsenic and subcutaneous injection of Ara-c.

Methods:

In this prospective study, elderly patients (including those who are older than 60 with comorbidity and all patients over 65 years of age), treatment-resistant patients (primary refractory) and relapsed patients who were not candidates for chemotherapy due to lack of compatible donors, randomly divided into two groups. Group A received treatment regimen consisted of Ara-c 20 mg/Bid (LDAC) by subcutaneousinjection 5 days each week and arsenic trioxide 10 mg/day by infusion over 2 hours for 10 days each month. Group B was administered Ara-c 20 mg/Bid (LDAC) 5 days each week. From September 2012 to December 2014, 42 patients have entered the study and then randomly assigned to one of the two study groups (22 in Group A, 20 in Group B).

The mean age was 52 years for group A and 59 years for group B (p= 0.124). 31% of the patients were female. 9.1% of patients in group A and 20% in group B had secondary AML (p= 0.4). Elderly participants included 31.8% and 45% of patients in groups A and B, respectively. Cytogenetic results were available for 88% of all cases. The results of the cytogenetic analysis in group A: 1 patient showed the presence of t (8; 21), 12 were found to have a normal karyotype, 2 showed a complex translocation, 1 had del (7), 1 demonstrated +8 and 3 had other chromosomal abnormalities. The results of the cytogenetic analysis in group B: 1 patient showed the presence of t (8; 21), 5 were found to have a normal karyotype, 5 showed a complex translocation, 2 had del (7), 2 demonstrated +8 and 1 had other chromosomal abnormalities.

Results:

BMA & B evaluation of 20 patients in group A on day +60 showed refractory disease in 5(25%) patients; 12(60%) had partial remission and 3(15%) had bone marrow hypoplasia. The results obtained from 14 patients in group B showed that 2 (14.3%) patients were refractory to treatment, 10 (71.4%) had partial remission, 1(7.1%) had bone marrow hypoplasia and 1 patient reached complete remission (p=0.48).

BMA & B evaluation of 18 patients in group A on day +120 showed no remission in 3 (16.75) patients, partial remission in 5 (27.8%) patients and complete remission in 10 (42.9%) subjects. The results obtained from 12 patients in group B demonstrated 4 (33.3%) patients with no remission, 6 (58.3%) with partial remission and 1 (8.3%) was in complete remission (p= 0.035). By June 2015, 15 (68.2%) patients in group A and 15 (75%) patients in group B had died, and 7 (31.8%) patients in group A and 5 (25%) patients in group B are still alive.

Conclusion:

The overall survival (OS) was 16 months in both groups and no statistically significant difference was observed in this variable between the two groups (1-36 months). Compared to other groups, the result of bone marrow aspiration and biopsy on day +120 obtained from patients who were in CR showed higher OS.