Haematologica
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The molecular links between inflammation and coagulation are unquestioned. Inflammation promotes coagulation by leading to intravascular tissue factor expression, eliciting the expression of leukocyte adhesion molecules on the intravascular cell surfaces, and down regulating the fibrinolytic and protein C anticoagulant pathways. Thrombin, in turn, can promote inflammatory responses. ⋯ Similarly, in solution, EPCR blocks factor Va inactivation without modulating reactivity with protease inhibitors. Thus, these endothelial cell receptors for the protein C system share many properties in common including the ability to be modulated by inflammatory cytokines. Current studies seek to identify the substrate for the APC-EPCR complex as the next step in elucidating the mechanisms by which the protein C pathway modulates the response to injury and inflammation.
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Clinical Trial
Time sequential chemotherapy for primary refractory or relapsed adult acute myeloid leukemia: results of the phase II Gemia protocol.
High-dose cytarabine (HDAra-C), mitoxantrone and etoposide are the mainstay of several active regimens against relapsed or refractory acute myelogenous leukemia (AML). We designed a phase II study to assess the efficacy and side effects of a time sequential application of mitoxantrone plus intermediate-dose Ara-C followed by HDAra-C plus etoposide (GEMIA) in adult patients with refractory or relapsed AML. ⋯ The GEMIA time sequential chemotherapy regimen appears effective in obtaining remissions in refractory and relapsed adult AML. The high toxicity seen, however, suggests that its design is amenable to further improvements, especially in more elderly patients. Since remissions are short-lived, more innovative post-remission strategies are needed.
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Trisomy 12 is the most common numerical chromosomal aberration in patients with B-cell chronic lymphocytic leukemia (B-CLL). Fluorescence in situ hybridization (FISH) has improved the detection of this cytogenetic abnormality and has made detection possible in all phases of the cell cycle. The presence of the trisomy 12 positive (+12) cell population has generally been investigated in leukemic cells obtained from the peripheral blood of CLL patients. To ascertain whether trisomy 12 is expressed homogeneously in cells of different hemopoietic tissues, we applied FISH to lymph node, peripheral blood and bone marrow samples obtained simultaneously from 23 untreated B-CLL patients. ⋯ Several previous reports show that only a proportion of malignant B-CLL cells carry trisomy 12 when analyzed by interphase FISH. The higher proportion of +12 cells in lymph nodes than in peripheral blood or bone marrow of CLL patients with trisomy 12 could reflect different cell distributions in different tissues, or lymph node specific tropism, or proliferative advantage in selected tissue. At present, the role of trisomy 12 in the pathogenesis of lymphoproliferative disorders is unclear.
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Clinical Trial Controlled Clinical Trial
Autologous blood stem cell transplantation for acute myeloblastic leukemia in first complete remission. Intensification therapy before transplantation does not prolong disease-free survival.
To compare the clinical results of two consecutive therapeutic protocols including autologous blood stem cell transplantation (ABSCT) for patients with de novo acute myeloblastic leukemia (AML) in first complete remission (CR1). ⋯ Our study confirms that AML patients in CR1 receiving ABSCT have rapid engraftment with low mortality. However, autologous transplants with PBSC collected after consolidation chemotherapy were still associated with a high rate of relapse (RR). This RR was not apparently reduced by the administration of intermediate dose Ara-C before transplantation.
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Clinical Trial Controlled Clinical Trial
Detection of focal myeloma lesions by technetium-99m-sestaMIBI scintigraphy.
The tracer tachnetium-99m-2-methoxy-isobutyl-isonitrile (Tc99m-sestaMIBI) has recently been shown to concentrate in some neoplastic tissues, including myeloma. We investigated the diagnostic capacity and limits of this procedure in tracing focal myeloma lesions, and compared them with those of conventional radiological procedures (Xr). ⋯ In untreated patients, the number of lesions revealed by Tc99m-sestaMIBI was comparable to that shown by Xr, while in pretreated patients Tc99m-sestaMIBI traced a number of lesions lower than that detected by Xr. The reason for this discrepancy is that Tc99m-sestaMIBI traces only active lesions. Tc99m-sestaMIBI limitations in identifying focal lesions may derive from the dimension of the smallest traceable lesion (about one centimeter), and from the possibility that focal plasma cell localizations in collapsed bone may not be visualized due to inadequate vascularization. Tc99m-sestaMIBI scintigraphy is an interesting tool for diagnosing, staging and following up focal myeloma lesions, in the bone as well as in soft tissues. It is more specific than conventional Xr in identifying sites of active disease.