Trends in Bone Marrow Sampling and Core Biopsy Specimen Adequacy in the United States and Canada: A Multicenter Study.

OBJECTIVES: To assess bone marrow (BM) sampling in academic medical centers. METHODS: Data from 6,374 BM samples obtained in 32 centers in 2001 and 2011, including core length (CL), were analyzed. RESULTS: BM included a biopsy (BMB; 93%) specimen, aspirate (BMA; 92%) specimen, or both (83%). The median (SD) CL was 12 (8.5) mm, and evaluable marrow was 9 (7.6) mm. Tissue contraction due to processing was 15%. BMB specimens were longer in adults younger than 60 years, men, and bilateral, staging, and baseline samples. Only 4% of BMB and 2% of BMB/BMA samples were deemed inadequate for diagnosis. BM for plasma cell dyscrasias, nonphysician operators, and ancillary studies usage increased, while bilateral sampling decreased over the decade. BM-related quality assurance programs are infrequent. CONCLUSIONS: CL is shorter than recommended and varies with patient age and sex, clinical circumstances, and center experience. While pathologists render diagnoses on most cases irrespective of CL, BMB yield improvement is desirable.

Therapy-related acute myelogenous leukemia with an 11q23/MLL translocation following adjuvant cisplatin and vinorelbine for non-small-cell lung cancer.

Cisplatin-based chemotherapy has become an accepted standard in the adjuvant treatment of non-small-cell lung cancer (NSCLC). We present a case of acute myelogenous leukemia with an 11q23/MLL rearrangement diagnosed 1 year after the completion of 4 cycles of cisplatin and vinorelbine for resected NSCLC. To our knowledge, this is the first case of therapy-related acute myelogenous leukemia (t-AML) associated with this chemotherapy combination. The literature on t-AML with the 11q23/MLL rearrangement is reviewed.

Rituximab-induced changes in hematolymphoid tissues found at autopsy.

The effect of rituximab on malignant B cells and normal circulating B cells has been previously studied. In contrast, data on the degree of depletion of nonneoplastic B cells induced by rituximab in lymph nodes and spleen is limited. For this purpose, clinical charts, autopsy records, lymph node and spleen sections, and immunoperoxidase stains were reviewed from 10 patients who had received 1 to 40 doses of rituximab before death. The percentage of nonneoplastic B cells was lower in the lymph node and spleen in rituximab-treated patients when compared with cyclophosphamide, doxorubicin, vincristine, and prednisone-treated patients and patients without lymphoma. The effect of rituximab on nonneoplastic B cells was observed as soon as 1 month after administration and with as few as 3 doses. Reappearance of normal numbers of B cells was not observed 1 to 12 months after the last dose of rituximab was administered. We conclude that rituximab induces prompt, consistent, profound, and prolonged depletion of B lymphocyte populations in human lymphoid tissue.

Localization of functional endothelin receptor signaling complexes in cardiac transverse tubules.

Endothelin-1 (ET-1) is an autocrine factor in the mammalian heart important in enhancing cardiac performance, protecting against myocardial ischemia, and initiating the development of cardiac hypertrophy. The ETA receptor is a seven-transmembrane G-protein-coupled receptor whose precise subcellular localization in cardiac muscle is unknown. Here we used fluorescein ET-1 and 125I-ET-1 to provide evidence for ET-1 receptors in cardiac transverse tubules (T-tubules). Moreover, the ETA receptor and downstream effector phospholipase C-beta 1 were co-localized within T-tubules using standard immunofluorescence techniques, and protein kinase C (PKC)-epsilon-enhanced green fluorescent protein bound reversibly to T-tubules upon activation. Localized photorelease of diacylglycerol further suggested compartmentation of PKC signaling, with release at the myocyte "surface" mimicking the negative inotropic effects of bath-applied PKC activators and "deep" release mimicking the positive inotropic effect of ET-1. The functional significance of T-tubular ET-1 receptors was further tested by rendering the T-tubule lumen inaccessible to bath-applied ET-1. Such "detubulated" cardiac myocytes showed no positive inotropic response to 20 nM ET-1, despite retaining both a nearly normal twitch response to field stimulation and a robust positive inotropic response to 20 nm isoproterenol. We propose that ET-1 enhances myocyte contractility by activating ETA receptor-phospholipase C-beta 1-PKC-epsilon signaling complexes preferentially localized in cardiac T-tubules. Compartmentation of ET-1 signaling complexes may explain the discordant effects of ET-1 versus bath applied PKC activators and may contribute to both the specificity and diversity of the cardiac actions of ET-1.