Survivorship In AML - Outcomes Of Acute Myelogenous Leukemia (AML) Patients (pts) After Maintaining Complete Remission (CR) For At Least 3 Years
Authors: Shetty Aditya , Kantarjian Hagop M , Champlin Richard E , Borthakur Gautam , Badar Talha , Garcia-Manero Guillermo , Andersson Borje S. , Oran Betul , Ciurea Stefan O. , Konopleva Marina , Andreeff Michael , Kornblau Steven M. , Wierda William G. , Pierce Sherry , Ravandi Farhad , Cortes Jorge E. 
Published: October 2019

Abstract

Introduction
Approximately 80% of younger patients and 50% of older patients with newly diagnosed AML achieve CR after induction chemotherapy. The majority of patients who achieve CR eventually relapse, with most relapsing within the first 3 years. Long-term outcomes in pts maintaining 1st CR for at least 3 years (AML survivors) remain largely unknown. The purpose of this study was to investigate long-term outcomes in this subset of pts.

Methods
We performed a chart review of pts with AML treated at our institution who achieved CR for at least 3 years after their initial chemotherapy ± allogeneic stem cell transplant (ASCT) to analyze their long-term outcomes.

Results
1792 pts with AML were treated between 2000 and 2010 at our institution. 1081 (60%) pts achieved CR. Among them, 266 (25%; 15% of all treated) maintained 1st CR for at least 3 years. The 1st 200 pts are described in this analysis: 33 after ASCT and 167 after chemotherapy (chemo) alone. Median time to CR from initiation of induction chemotherapy was 34 days (range, 19-115) for pts who received ASCT and 28 days (17-104) for chemo only. Characteristics of AML survivor pts at time of diagnosis were as follows: hypertension (HTN) was present in 25% of the pts; cardiac disease in 7%; hypothyroidism in 5%; diabetes (DM) in 7%; depression in 6%; osteoporosis in 2%; chronic obstructive disease (COPD) or asthma in 4%. Median number of medications per pt at baseline was 1 (0-7). Relapses after maintaining CR for ≥3 years (i.e., late relapses) were noted in 12% of the pts: 9% of the pts treated with ASCT and 12% of pts with chemo alone. The median CR duration for those who relapsed was 4 years (3-10) and 4.8 years (3-12), respectively. At relapse, karyotype was different from the karyotype at the time of diagnosis in 47% of the cases: 100% after ASCT and 41% after chemo alone. Mutational status changes at relapse were noted in 31% of the pts. New Flt3 ITD mutations were the most common change, noted in 75% of pts who had a mutational status change. A 2nd complete remission (CR2) was achieved in 52% of pts, including 33% of pts that had received ASCT and 56% of pts treated with chemo alone. The median CR2 duration was 5 months and 10 months (3-30) respectively. The median survival after relapse was 13 months (1 to 42). Four pts with relapsed disease who initially were treated with chemo only underwent ASCT; no patient received a 2nd ASCT. New medical problems that were present at the 3 year mark included: HTN in 10% of pts; cardiac disease in 4%; hypothyroidism in 4%; depression in 4%; renal insufficiency in 3%; pulmonary disease in 2%; DM in 3%; hematological disorders, including anemia, thrombocytopenia, monoclonal gammopathy of undetermined signigicance (MGUS), systemic mastocytosis & Waldenstorm’s macroglobulinemia, in 5%. Pulmonary disorders (e.g., bronchiolitis obliterans and COPD) occurred in 6% of pts who underwent ASCT and 2% of pts who treated with chemo alone. Renal insufficiency was noted in 9% of pts who underwent ASCT and in 2% of pts treated with chemo alone. The median number of medication per pt 3 yrs from initial CR was 3 (range, 0-11). New medical problems that developed at time of last follow up included: HTN in 12% of pts, cardiac disease in 6%, hypothyroidism in 5%, depression in 7%, renal insufficiency in 4%, pulmonary disease in 3%, DM in 5%, hematological disorders in 6%. Cardiac problems, including the development of coronary artery disease, myocardial infarction, congestive heart failure and arrhythmias were noted in 3% of pts who underwent ASCT and in 6% of pts treated with chemo alone. The median number of medications per pt at last follow up was 3 (0-14). Second malignancies occurred in 10% of pts. The most common 2nd malignancies were colorectal carcinoma, breast cancer, prostate cancer and lymphoma, each occurring in 2% of pts. At median follow up of 4.2 years (3.2-10.2) and 4.9 years (3.2-12) respectively, 94% and 80% of pts are alive. In descending order, the most common causes of death included AML relapse, second malignancy and myocardial infarction.

Conclusion
AML pts who achieved CR for at least 3 years have a low incidence of late relapses. New medical problems including heart disease and second malignancies may occur but most pts are still currently alive. AML pts who maintain 1st CR for at least 3 years require ongoing medical care and long-term surveillance.

Disclosures:
No relevant conflicts of interest to declare.