Non-specific interstitial pneumonia as the initial presentation of biphenotypic acute leukemia: a case report

Nonspecific interstitial pneumonia has been linked to numerous etiologies including, most recently, haematologic malignancy. We present a 46-year-old woman with recent-onset rheumatologic illness who developed pulmonary symptoms as the presenting feature of biphenotypic acute leukaemia. Chest radiology demonstrated bilateral infiltrates, and lung biopsy revealed nonspecific interstitial pneumonia. Corticosteroid therapy resulted in resolution of both her pulmonary and rheumatologic symptoms, and her pulmonary symptoms did not recur following treatment of her leukemia. The case highlights the importance of searching for an underlying etiology when confronted with nonspecific interstitial pneumonia

GAS6 Induces Axl-mediated Chemotaxis of Vascular Smooth Muscle Cells

Atherosclerosis and arterial restenosis are disease processes involving the accumulation of vascular smooth muscle cells following vascular injury. Key events leading to these processes are migration and proliferation of these cells. Here, we demonstrate that GAS6, encoded by the growth arrest-specific gene 6, induces a directed migration (chemotaxis) of both rat and human primary vascular smooth muscle cells while showing only marginal mitogenic potential in human vascular smooth muscle cells. GAS6 stimulation induces Axl autophosphorylation in human vascular smooth muscle cells, indicating that specific GAS6-Axl interactions may be associated with GAS6-directed chemotaxis. To test this hypothesis, vascular smooth muscle cells overexpressing Axl were generated by gene transfer and assessed for their ability to migrate along a GAS6 gradient. These Axl overexpressors exhibited 2-5-fold increased sensitivity to GAS6-induced chemotaxis. Furthermore, vascular smooth muscle cells expressing the kinase dead mutant of Axl or exposure to the soluble Axl extracellular domain showed attenuated GAS6-induced migration. Taken together, these results suggest that GAS6 is a novel chemoattractant that induces Axl-mediated migration of vascular smooth muscle cells. The separation of mitogenesis from migration provided by this study may enhance the molecular dissection of cell migration in vascular damage

Bortezomib Added to Daunorubicin and Cytarabine During Induction Therapy and to Intermediate-Dose Cytarabine for Consolidation in Patients With Previously Untreated Acute Myeloid Leukemia Age 60 to 75 Years: CALGB (Alliance) Study 10502

The purpose of this study was to determine remission induction frequency when bortezomib was combined with daunorubicin and cytarabine in previously untreated older adults with acute myeloid leukemia (AML) and safety of bortezomib in combination with consolidation chemotherapy consisting of intermediate-dose cytarabine (Int-DAC)

Phase I study of the aurora A kinase inhibitor alisertib with induction chemotherapy in patients with acute myeloid leukemia

Aberrant expression of aurora kinase A is implicated in the genesis of various neoplasms, including acute myeloid leukemia. Alisertib, an aurora A kinase inhibitor, has demonstrated efficacy as monotherapy in trials of myeloid malignancy, and this efficacy appears enhanced in combination with conventional chemotherapies. In this phase I, dose-escalation study, newly diagnosed patients received conventional induction with cytarabine and idarubicin, after which alisertib was administered for 7 days. Dose escalation occurred via cohorts. Patients could then receive up to four cycles of consolidation, incorporating alisertib, and thereafter alisertib maintenance for up to 12 months. Twenty-two patients were enrolled. One dose limiting toxicity occurred at dose level 2 (prolonged thrombocytopenia), and the recommended phase 2 dose was established at 30mg twice daily. Common therapy-related toxicities included cytopenias and mucositis. Only three (14%) patients had persistent disease at mid-cycle, requiring “5+2” reinduction. The composite remission rate (complete remission and complete remission with incomplete neutrophil recovery) was 86% (nineteen of twenty-two patients; 90% CI 68–96%). Among those over age 65 and those with high-risk disease (secondary acute leukemia or cytogenetically high-risk disease), the composite remission rate was 88% and 100%, respectively. The median follow up was 13.5 months. Of those treated at the recommended phase 2 dose, the 12-month overall survival and progression-free survival were 62% (90% CI 33–81%) and 42% (90% CI 17–65%), respectively. Alisertib is well tolerated when combined with induction chemotherapy in acute myeloid leukemia, with a promising suggestion of efficacy. (clinicaltrials.gov Identifier:01779843)