Human Immunodeficiency Virus (HIV)-Associated Acute Myeloid Leukemia (AML) in the Era of Highly Active Antiretroviral Therapy (HAART): High Complete Remission Rate, but Poor Tolerance of Consolidation Therapy and Short Disease-Free Survival.

Abstract 4126

HIV-infected patients have a significantly longer life expectancy in the era of HAART, but also have an increasing incidence of malignancies. A 2.5-fold increase in leukemia (Patel et. Al., Annals of Int Med. 2008, 148:728-736) has been documented in HIV-infected individuals, including a two-fold increase in AML incidence, with a predominance of M2 and M4 subtypes (Aboulafia et. al., AIDS 2002, 16:865-876 and Sutton et. al., Br J Hematol 2001,112:900-908). To further characterize the biology and outcome of AML in HIV-infected patients in the HAART era, we reviewed the experience with these patients at the University of Maryland Greenebaum Cancer Center and the Johns Hopkins Kimmel Cancer Center. All patients were from greater Baltimore, a city with 37.7 new HIV cases per 100,000 population, the second highest among U.S. cities (Baltimore City HIV/AIDS Statistics Fact Sheet, April 18, 2008. Department of Health and Mental Hygiene, State of Maryland). After IRB approval was obtained, cases were identified by review of all AML patients seen at both institutions between 2002 and 2009. Data regarding patient age, gender, white blood cell count, AML subtype, karyotype, FLT3 mutation analysis, HIV treatment, CD4 count, HIV viral load, AML treatment and treatment outcome were collected. We report 8 HIV-positive AML patients diagnosed and treated in Baltimore, Maryland in the HAART era. Six patients had M2 or M4 subtype (four M2, two M4, one M1 and one M5). One M2 patient had t(8:21) and one M4 patient had inv(16); other abnormalities included del(7p) in one M4 patient, a complex karyotype in two M2 patients, one of whom had treatment-related AML. Three patients had a normal karyotype. FLT3 was wild-type in six patients, and was not studied in two. All but one patient had CD4 counts below 200 cells/μL. HAART was incorporated into the treatment of seven of our eight patients. Multiple HAART regimens were used, and treatment was variable. One patient received HAART during induction, but not consolidation. The other seven patients started or resumed HAART at some point during consolidation. AML was not treated in one patient who had rapidly progressive multiorgan failure at AML presentation. Seven patients were treated with standard induction chemotherapy; six achieved complete remission (CR), while one had refractrory disease. All six patients received consolidation with high-dose cytarabine. Complications during consolidation therapy included prolonged neutropenia in three patients, subdural hematoma secondary to prolonged, severe thrombocytopenia in one patient, and cerebellar toxicity in one patient. Disease-free survival (DFS) ranged from 15 weeks to 20 months, with a median of 10 months. One patient developed diffuse large B-cell lymphoma following completion of consolidation therapy. CD4 count, viral load and treatment of HIV did not correlate with ability to tolerate consolidation, nor with DFS. We conclude that HIV-infected AML patients achieve CR, but have poor tolerance of consolidation therapy and short DFS. Based on our data and the literature to date, CBF abnormalities may occur at an increased rate in these patients, but are not associated with favorable outcomes. Further investigation is needed to substantiate a relationship between HIV and CBF mutations, and to develop treatment strategies for AML therapy, HAART and supportive care to improve outcomes.