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To determine how patient race, ethnicity, and degree of poverty affect treatment and survival for acute myeloid leukemia (AML).A linked database of the Florida cancer registry and State inpatient and outpatient hospital data for 1998-2002 was queried. Effects of demographic and treatment characteristics on survival were explored using univariate and multivariate analyses methods.A total of 4659 patients with AML were identified. Over 50% of patients with AML were 70 years of age or older. African American (AA) patients were diagnosed at significantly younger ages than were whites (P0.001). In multivariate analysis, independent predictors of worse survival in AML were aged over 50 (hazard ratios [HRs]: 1.60, 2.15, 3.04, and 3.62 over the decade-cohorts, all P0.001), AA race (HR: 1.27, P0.001), being a former or current user of tobacco (HR: 1.13, P = 0.004 and HR: 1.28, P0.001, respectively), residing in an area with the highest poverty level (HR: 1.15, P = 0.007), and being covered only by Medicaid (HR: 1.23, P = 0.014). No differences in outcomes were observed related to gender or ethnicity. Receipt of chemotherapy was strongly associated with improved survival (HR: 0.59, P0.001). When only those patients who received and appeared to respond to treatment are included, AAs continued to demonstrate a worse outcome than Whites.AML disproportionately affects the elderly. AA patients and patients from poorer communities with AML have significantly worse survival. Interventions to provide earlier diagnosis in these patients as well as to improve overall outcomes are needed to address these disparities.

Aminobisphosphonates have shown significant antitumor activity in vitro and in vivo with selective pharmacodistribution to bone, and an established role in the treatment of malignant bone disease. Given that the mode of action of aminobisphosphonates involves decreasing the prenylation of the Rho family of proteins, through decreasing the availability of prenyl groups (farnesyl and geranylgeranyl isoprenoids), the authors sought the inhibition of Rho protein prenylation at two points, by using an aminobiphosphonate (alendronate) in conjunction with a prenyl transferase inhibitor (R115777, a specific farnesyl transferase inhibitor with limited effects in geranylgeranyl transferase). The authors show synergistic inhibition of the prenylation dependent membrane association and migratory function of Rho proteins, translating into a suppressive effect on in vitro tumor cell invasiveness and in vivo metastasis. The findings support the use of aminobisphosphonates in conjunction with farnesyl transferase inhibitors in the prevention of metastatic progression and suggest that metastatic progression is a valid end point in assessing the antitumor activity of farnesyl transferase inhibitors.

OBJECTIVE Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) are closely related human retroviruses. HTLV-I has been implicated in a chronic progressive myelopathy, known as tropical spastic paraparesis (TSP) or HTLV-I-associated myelopathy (HAM). We sought to determine whether autoantibodies to brain antigens were present in the cerebrospinal fluid (CSF) of a patient with chronic progressive spastic myelopathy with evidence of both HIV-1 infection and HTLV-I/II seropositivity. DESIGN A 54-year-old bisexual man with clinical features of HAM/TSP of over 20 years' duration was followed. METHODS We applied discriminatory DNA amplification (polymerase chain reaction) to distinguish HTLV-I from HTLV-II and to verify co-infection with HIV-1. The patient's CSF was used to screen a human brain cDNA expression library to identify antibodies directed against brain antigens. Autoreactive bacteriophage clones were isolated and sequenced. RESULTS The patient was found to be co-infected with both HIV-1 and HTLV-II, but not with HTLV-I. HTLV-II proviral levels in the peripheral blood remained relatively constant, despite therapy with zidovudine. Prominent oligoclonal banding of immunoglobulins was present in the patient's CSF. A single repeatedly reactive cDNA clone was identified, by screening with CSF antibody, sequenced, and found to be the human homologue of the rat insulinoma gene, rig. CONCLUSIONS HTLV-II infection may predispose to development of a HAM/TSP-like illness. Autoimmune mechanisms, such as autoantibody formation, may play a role in pathogenesis.