Hepatic iron overload, a possible consequence of treatment with imatinib mesylate: a case report

Imatinib, a tyrosine kinase inhibitor has revolutionized the therapy of Philadelphia chromosome positive chronic myeloid leukemia. Side effects of imatinib include grade 1-4 hepatotoxicity in a subset of patients. We report the case of a 46-year-old male with chronic myeloid leukemia, who developed hepatic hemosiderosis during treatment with imatinib. After ruling out the established congenital and acquired causes of hepatic hemosiderosis, we attribute this to a possible side effect of imatinib therapy. This condition was successfully treated with periodic phlebotomy thus precluding discontinuation of imatinib. To our knowledge, this is the first report of hepatic hemosiderosis most likely consequent to imatinib therapy

Kinetics of Measures Guiding Decongestive Therapy in AHF: Comparison of Lung Ultrasound to Conventional Markers

Introduction: Lung ultrasound (LUS) scoring of pulmonary edema severity has been proposed as a marker to track treatment response in acute heart failure (AHF), with a hypothetical advantage of detecting changes in congestion more quickly than traditional markers of treatment response. We compared change in LUS congestion score to contemporaneous changes in daily weight, natriuretic peptides, subjective score of worst AHF symptom (WSS), and clinical/exam findings in hospitalized heart failure patients from ED arrival to discharge, to determine which measure showed the most dynamic reduction during decongestive therapy. Methods: This is a preliminary analysis of an ongoing prospective observational cohort study. ED patients were enrolled if they were being treated for presumed AHF diagnosis and if a LUS met diagnostic criteria for pulmonary edema. LUS, BNP, body weight, WSS, and clinical congestion score (CCS) (calculated based on orthopnea, JVD, hepatomegaly, and peripheral edema) were assessed at ED arrival and daily through discharge. Random effects models of percent change were fit for each measure, adjusted for initial value, to estimate magnitude and speed of change during ED and in-hospital decongestion. Results: 78 observations of 21 patients were analyzed. Median age and NYHA score were 66 y/o and 4, respectively. LUS score dropped the most quickly, showed greatest mean change from ED to discharge, and showed the greatest change prior to transition to PO diuretics (initial 24-60 hours). BNP did not fall below ED values until day 3, and did not reach its nadir until day 6. The CCS correlated well with LUS, but showed a smaller magnitude of change from ED to discharge. Weight and WSS showed no significant change. Conclusions: LUS score showed a more rapid and larger change in response to diuretic therapy, suggesting it may be a more dynamic measure of decongestion than conventional measures of treatment efficacy

A donor-derived asialo-GM1+ cell induces depression of B-cell genesis during systemic graft-versus-host disease

The nature of the effector cell(s) responsible for the depression of B- cell genesis in the bone marrow of mice undergoing systemic graft- versus-host disease (GVHD) has been examined. Donor C57BL/6 (B6) mice were treated in vivo with either a single injection of anti-asialo GM1 antibody (anti-ASGM1) to eliminate naturally occurring (endogenous) ASGM1+ cells or B6xAF1 (B6AF1) lymphoid cells followed by anti-ASGM1 to eliminate both endogenous and “induced” ASGM1+ cells. Lymphoid cells from donor mice after the elimination of endogenous ASGM1+ cells produced severe GVHD and concomitant depression of B-cell genesis when injected into B6AF1 recipients. In contrast, cells from donors depleted of both the endogenous and inducible ASGM1+ populations did not cause GVHD or depletion of B lineage cells in B6AF1 recipients but did depress B-cell genesis in B6C3F1 mice. The “induced” ASGM1+ cells were Thy 1+, but their elimination did not significantly alter either overall T-cell function or specific cytotoxic T-cell (CTL) reactivity against the sensitizing (B6AF1) strain. The results suggest that the effector cell responsible for the depression of B-cell genesis during systemic GVHD can be induced to express ASGM1, is strain-specific and Thy 1+; but is not a conventional CTL.</jats:p