Patients with refractory and relapsed acute myeloid leukemia (AML) have relatively unfavorable prognoses and require innovative therapeutic approaches. We evaluated the efficacy and toxicity profiles of homoharringtonine (HHT), cytarabine (Ara-c) and aclarubicin combination chemotherapy in 46 refractory and/or relapsed AML patients between February 2004 and December 2009.
Eleven cases were primary refractory disease and rest of them had relapsing disease. After one course of HAA treatment, complete remission (CR) was achieved in 35 of 46 patients (76.1%), while 3 cases showed partial remission (PR) (6.5%) and 8 cases (17.4%) had resistant to this regimen. One PR and one NR patient obtained CR after second course of HAA, yielding a total CR rate was 80.4%. Hematological toxicity was the most prominent toxicity of this regimen. Grade IV hematologic toxicity occurred in 91.3% cases. Neutrophil recovery time was 13 (5–60) days. Nonhematologic complications were mild to moderate nausea, vomiting, and mucositis and could be controlled by routine measures. Early death (ED) did not occur in these 46 patients.
There was no correlation between response rate and leukemia subtype (AML FAB subtype), leukocyte, blast count in bone marrow, platelet count and sex (P >0.05). However, poor karyotype and age (≥45 years old) were factors associated with increased risk of treatment failure. Of the 46 patients, one patient, who upon achieving CR after the first re-induction therapy refused further treatment, was ultimately lost to follow-up. The median overall survival rate (OS) was 29 (2–86) months in 45 cases. Relapse-free survival (RFS) was 36 (0.5–85) months in 36 CR cases. By the time of closeout, the estimated 3-year OS rate was 42% for all 45 cases, and 43% estimated RFS at 3 years for the 36 cases of CR. OS and RFS were influenced by leukemia-related factors and disease status: Hb <10g/dl and poor karyotype in both univariate and multivariate analyses.
Allogeneic stem cell transplantation was performed in 7 patients and all achieved CR, but 1 patient died of GVHD, 2 died of pneumonia, 1 relapsed followed by death and another 3 are still alive with CR. At present, 19 patients are still alive and 18 of these are in continuous remission with one alive with leukemia. The rest (26/45) of the patients are all deceased.
In conclusion, HAA is a good choice in cases with refractory/relapsing AML for salvage chemotherapy, preferably with a high efficacy and low-toxicity profile.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.