Increased mean platelet volume and immature platelet fraction as potential predictors of thrombotic complications in BCR/ABL-negative myeloproliferative neoplasms.

BCR/ABL-negative myeloproliferative neoplasms (MPNs) are considered to be acquired thrombophilic conditions. Persistently enhanced platelet activation has been described in polycythaemia vera and essential thrombocythaemia (ET), and shown to contribute to a higher risk of arterial and venous thrombotic complications. Recent studies have shown that mean platelet volume (MPV) and immature platelet fraction (IPF) can serve as useful markers of platelet activation and increased risk of thrombosis. The aim of the present study was to investigate the relationship between these parameters and thrombotic events in BCR/ABL-negative MPN. MPV values in patients with BCR/ABL-negative MPN were significantly higher than MPV values of healthy individuals (P < 0.001). No significant difference in MPV or IPF was observed between groups of patients with and without thrombotic complications (P = 0.441; P = 0.110); the difference in IPF values was close to the significance level for patients with ET (P = 0.073). Higher values of IPF were more frequently detected in patients with JAK2 V617F positivity (P = 0.030). These patients had higher MPV more frequently than others, and this difference was close to the significance level (P = 0.056). Further studies should validate the use of platelet parameters to identify patients at high risk.

Inactivation of p53 and amplification of MYCN gene in a terminal lymphoblastic relapse in a chronic lymphocytic leukemia patient.

B-cell chronic lymphocytic leukemia (CLL) is an incurable disease with a highly variable clinical course. A proportion of patients eventually progress to a higher stage of malignancy. A recent association has been observed between the presence of aberrant somatic hypermutations in leukemic cells (hypermutations occurring outside of the immunoglobulin locus) and the transformation to a diffuse large B-cell lymphoma or prolymphocytic leukemia. In this study, we report on the rarely observed blastic transformation in a CLL patient who had previously been shown to harbor aberrant somatic hypermutations in the TP53 tumor-suppressor gene (Mol Immunol 2008;45:1525-29). The enzyme responsible, the activation-induced cytidine deaminase, was still active within the transformation, as evidenced by the ongoing class-switch recombination of cytoplasmic immunoglobulins. The transformation was accompanied by a complete p53 inactivation, as well as complex karyotype changes including prominent amplification of MYCN oncogene. Our case-study supports the view that the aberrant somatic hypermutation is associated with transformation of CLL to a more aggressive malignancy.

Treatment of chronic myeloid leukemia with autologous transplantation using peripheral blood stem cells or bone marrow cultured in IL-2 followed by IL-2, GM-CSF, and IFN-alpha administration.

Interleukin-2 (IL-2) is able to generate nonspecific cytotoxic effectors from hematopoietic precursors. We evaluated the feasibility and efficacy of chronic myeloid leukemia (CML) treatment with autologous hematopoietic stem cell transplantation (HSCT) using grafts cultured in IL-2 followed by immunotherapy with IL-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), and interferon (IFN)-alpha. Eight patients with CML were enrolled: five in an accelerated phase and three in a chronic phase. They received peripheral blood stem cells (PBSC) or bone marrow (BM) cultured in a medium containing IL-2 for 24 h. A median of 1.29 x 10(6) CD34+ cells/kg were infused after conditioning with busulfan (12 16 mg/kg) in PBSC recipients. BM was infused without prior myeloablative therapy. The engraftment occurred with a median of 15 d. Engraftment failure developed in one patient. The transplantation was followed by a 1-mo regimen of IL-2 (0.5 x 10(6) IU/m(2) daily) and GM-CSF, and 6 mo of IFN-alpha. One complete and one transient minor cytogenetic remission were observed. At 24 mo after transplantation, two patients had died of progressive disease and one of infection. Five patients had stable disease in the chronic phase. Autologous transplantation using IL-2-activated graft is feasible and the subsequent IL-2, GM-CSF, and IFN-alpha administration has acceptable toxicity. However, no benefits in comparison with conventional autologous transplantation for CML were identified in our study.