Low-dose cytarabine and cladribine for treatment of relapsed or refractory acute myeloid leukemia: clinical experience
Sergej V. Gritsaev, Ivan I. Kostroma, Anastasia A. Kuzjaeva, Irina M. Zapreeva, Elena V. Litvinskaya, Lubov V. Steljmashenko, S. A. Tiranova, Irina S. Martinkevitch, Nadezhda A. Potichonova, Kudrat M. Abdulkadyrov.
Russian Research Institute of Hematology and Transfusiology, St.-Petersburg
Summary
The aim of this study was to evaluate the efficiency of low-dose cytarabine (Ara-C) combined with cladribine for treatment of relapsed/refractory acute myeloid leukemia (AML) and to determine the factors associated with response to the therapy. Patients and Methods. We have analyzed clinical data of the ten AML patients (26 to 58 years old; median, 48), with the following diagnoses: de novo AML (n=7); secondary AML (n=2), and refractory anemia with excess of blasts (RAEB-2, n=1). Four patients had refractory AML; clinical relapse was revealed in three cases. The ‘7+3’ induction regimen was ineffective in the RAEB-2 patient. There was no response to any therapy applied in the patients with secondary AML. The treatment schedule consisted of Ara-C (10-15 mg/m2 SC twice a day for 1-14 d), and cladribine (5 mg/m2 IV for 1-5 d). The course should be repeated in cases of >50% decrease in marrow blast counts.
Results
According to the protocol, the patients underwent 1-2 courses of the treatment. All the patients received cladribine, according to the protocol. This protocol lasted from 7 to 21 days, depending on the patients’ status or severity of complications. Two patients achieved complete response (CR) and 3, or partial response (PR). Myelosupression was the common complication. All the patients received blood transfusions. The duration of response was 2 to 3 mo. Allogeneic stem cell transplantation was performed in 2 patients with CR. Noteworthy, AML progression in one patient was confirmed at the start of conditioning regimen. All the patients with CR and PR were initially diagnosed with de novo AML; there were no FLT3 or c-KIT mutations, and duration of therapeutic course was >10 days. Conclusion. Low-dose Ara-C combined with cladribine may be a treatment option for some patients with relapsed or refractory de novo AML without FLT3 or c-KIT mutations.
Keywords
Acute lymphoblastic leukemia, refractory, cytarabine, cladribine
