PB1838: TOXICITY AND OUTCOME OF HIGH DOSE CYTARABINE (18 G/M2) FOR AML CONSOLIDATION.

Abstract

Background: The combination of an anthracycline and cytosine arabinoside has been the standard induction therapy in adults with acute myeloid leukemia (AML). After complete remission (CR), a post-remission therapy is necessary. CALGB study in 1994 established high dose cytarabine as one of the standard regimens. However, the current 2017 European LeukemiaNet recommendations for AML discourage the use of HIDAC, because intermediate doses of cytarabine (1-1.5g/m2) may be as effective. Hereby we present retrospective data of AML patients treated with HIDAC after the first CR (CR1). Aims: The main purpose of this study was to determine the toxicities rates of patients receiving HIDAC. Methods: Adult patients with a diagnosis of AML, who received at least one cycle of HIDAC after achieving first complete remission (CR1) were included. The study was conducted at University Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro (UFRJ), Brazil. Complete remission (CR) was defined using standard criteria. Patients in CR1 received consolidation chemotherapy consisting of cytarabine 3 g/m2 given by 3-hour IV infusion every 12 hours on days 1, 3, and 5 (18g/m2 per course). A minimum of 2 HIDAC courses and a maximum of 4 courses were usually planned. Results: From April 2008 to September 2020, 29 AML patients in CR1 received a total of 67 courses of HIDAC. The median age was 36 years (range, 18 to 62), and (41%) were females. Normal karyotype was present in 11 patients; five cases of CBF AML were identified: four t(8;21) and one t(16;16) with trisomy 22. The median number of cycles of consolidation was 2; 4 patients (14%) received 4 cycles, 10 received 3 cycles, 10 received 2 cycles and 5 received just 1 cycle. The overall survival was 16 months in patients who received 1 or 2 cycles (15 patients) and not reached in patients who received 3 or 4 cycles (14 patients). No significant differences in survival were observed according to the number of cycles (P=0.095). Granulocyte-colony stimulating factor (G-CSF) was given after 65 cycles (95.5%). The most common side effect was febrile neutropenia 38 (56.7%). Neurotoxicity was documented after 2 cycles. One patient presented with seizures on day 2 of the first cycle, and another patient presented with diplopia, abnormal coordination (dismetry) and visual blurring on the 10th day of the first cycle. Other significant side effects included: severe bleeding 8 (11.9%); mucositis 10 (15%), severe mucositis 1 (1.5%); nausea or vomiting 16 (23,9%); diarrhea 8 (11.9%), short duration diarrhea 5 (7.5%), diarrhea with dehydration 2 (3%), diarrhea with necessity of treatment 1 (1.5%); neutropenic enterocolitis 3 (5.5%); renal failure 3 (4.5%), hemodialysis 1(1.5%). Two deaths occurred before any documentation of relapse (TRM of 6.8%). One death occurred in the first cycle (day 15) due to Candida tropicalis candidemia and another after neutropenic enterocolitis (day 20). Discharge shortly after HIDAC was possible in 45 cycles (67.5%) and no readmission was required in 14 (20.9%). Readmission was necessary after 31 cycles (46.2%) and the median days at home was 5.8 (range, 3 to 8). Summary/Conclusion: HIDAC (18 g/m2) can be safely given to select AML patients after CR1. Our analysis demonstrates febrile neutropenia was the most common adverse event, neurologic toxicities were reversible and treatment related mortality occurred during early cycles. Hospital discharge after a HIDAC cycle is safe with the use of G-CSF.