Treatment Results of Intensive Chemotherapy for Higher-Risk Myelodysplastic Syndrome (HR-MDS) and Acute Myeloid Leukemia Related to MDS (MDS-AML)

Abstract 2934 Background: Since MDS is more prevalent in the elderly, use of intensive chemotherapy is considered to be difficult. However, granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF), use of clean room and development of promising antifungal agents have resulted in dramatically enhanced safety of post-chemotherapy control of elderly patients. Thus, we attempted to use intensive chemotherapy in HR-MDS and MDS-AML patients. Objectives: To evaluate, in HR-MDS and MDS-AML patients, the efficacy and safety of remission induction therapy and post-remission therapy that are standard treatment for de-novo AML in our department.This study enrolled 213 consecutive patients initially treated at our department between 2000 and 2010 who suffered MDS-related disease and whose survival was expected to be less than several months with supportive therapy alone. Almost all of the patients had ≥20% myeloblasts. The age of the patients ranged from 16 to 93 years (median: 70 years). They comprised 2 with good prognosis, 107 with intermediate prognosis and 104 with poor prognosis based on chromosomal findings. Methods: Remission induction therapy consisted of behenoyl-ara-C (BHAC) 350 mg/m 2 (300 mg/m 2 for patients aged ≥70 years) over 10 days and idarubicin (IDA) 12 mg/m 2 (10 mg/m 2 for patients aged ≥70 years) over 4 days. Additional etoposide 100 mg/m 2 over 4 days was given if bone-marrow examination on Day 15 revealed residual myeloblasts of ≥5%. The efficacy of the therapy was evaluated after the first course. Patients showing maintained remission received 8 courses of post-remission therapy over 11 months. This post-remission therapy included high-dose cytarabine (2 g/m 2 , or 1g/m 2 for patients aged ≥60 years) (HDAC) × 10 and mitoxantrone (MIT) 7mg/m 2 × 3 given initially after remission. Maintenance/intensification therapy mainly consisted of BHAC 350 mg/m 2 × 4 plus aclarubicin (ACR) 20 mg/body × 6 or IDA 10 mg × 1 alternately every 5 weeks. Outpatient maintenance therapy consisted of M-CSF over 7 days after the end of chemotherapy, followed by administration of G-CSF until neutrophil recovery. Patients were admitted to a clean room if WBC became 3 . As post-remission therapy, 90 patients received HDAC-MIT, while 50 did not. A total of 28 patients received bone-marrow transplantation during chemotherapy. Results: CR and PR were achieved in 146/213 (68%) and 43/213 (20%) patients, while 14/213 (7%) showed no response (NR) and 10/213 (5%) died during chemotherapy (CD). CR rate was comparable between patients aged ≥70 years (76/110, 69%) and those aged Conclusion: The results of this single-center clinical study indicate that major improvement of supportive therapy may allow introduction of remission safely and at a high probability in elderly patients with HR-MDS or MDS-AML. There remains a challenge since the median OS in patients with remission was still as short as around 1 year. One of the future challenges is how to use intensive chemotherapy in combination with distinctive new antileukemics such as lenalidomide. Disclosures: No relevant conflicts of interest to declare.