Syndrome of inappropriate secretion of antidiuretic hormone associated with imatinib.

OBJECTIVE: To describe a patient with Bcr-abl(+) acute lymphoblastic leukemia who developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) while being treated with high-dose imatinib. CASE SUMMARY: A 29-year-old woman was diagnosed with Bcr-abl(+) acute lymphoblastic leukemia, and treatment was initiated with chemotherapy and imatinib 800 mg daily. Following imatinib initiation, a gradual decrease in serum sodium level was noticed. Prolonged aplasia and neutropenic fever prompted discontinuation of therapy for 4 weeks. Following the patient's recovery, complete remission was achieved and monotherapy with imatinib 800 mg daily was restarted; however, hyponatremia recurred a few days later. The clinical findings and laboratory workup were compatible with the diagnosis of SIADH, which was attributed to high-dose imatinib. Fluid restriction and imatinib dosage reduction (to 600 mg/day) restored sodium levels. According to the Naranjo probability scale, this adverse reaction was probably associated with imatinib. DISCUSSION: Imatinib emerged as the first tyrosine kinase inhibitor to enter everyday clinical practice for the treatment of Ph(+) leukemias. Due to its molecular specificity, imatinib lacks the broad cytotoxicity of conventional chemotherapy. Inhibition of kinases in normal tissues accounts for many of imatinib's adverse reactions. To our knowledge, this is the first reported case of imatinib-induced SIADH. CONCLUSIONS: We recommend monitoring for SIADH if a patient receiving high-dose imatinib develops hyponatremia.

Platelet production and related pathophysiology in acute myelogenous leukemia at first diagnosis: prognostic implications.

Among various laboratory and clinical features megakaryocytopoiesis and platelet (PLT) counts have been previously insufficiently evaluated for their prognostic significance in acute myelogenous leukaemia (AML). We studied several clinical and laboratory features of 108 first diagnosed AML patients in relation with their prognosis. Patients with favourable prognostic features were excluded from the study. This study focused on the prognostic impact of PLT counts and related molecular biology in AML patients at initial diagnosis. In particular, the PLT counts were correlated with the endogenous production of thrombopoietin (TPO), c-mpl expression, CD34+ leukemic blast cell proportion, cytogenetics, and a prognostic correlation was established. We found that the most favorable prognosis appeared in the AML patient group with PLTs <25x10(9)/l and correlated to cytogenetic findings (normal or abnormal karyotypes), while by far the most unfavorable prognosis was found in the patient group with PLTs > or =130x10(9)/l independent of the corresponding cytogenetics. It was demonstrated that AML patients with normal or elevated PLT counts at first presentation, may constitute a distinct patient group with particular characteristics such as higher levels of endogenous TPO production, high expression of CD34+ leukemic blast cells, higher expression of c-mpl and consequently low response to chemotherapy and a very poor prognosis. These correlations between PLTs production (megakaryothrombopoiesis), TPO serum levels and TPO receptor (c-mpl) expression may help in the determination of risk-adapted AML patient groups and of targeted therapeutic strategies.

A clinicopathological study of B-cell differentiation markers and transcription factors in classical Hodgkin's lymphoma: a potential prognostic role of MUM1/IRF4.

BACKGROUND AND OBJECTIVES: Although most patients with classical Hodgkin's lymphoma (CHL) are cured, a significant minority are refractory to treatment. The investigation of biological markers could improve the predictive capacity of clinical staging systems. The aim of our study was to detect B-cell differentiation markers and transcription factors in CHL in order to define subgroups with different histogeneses and prognoses. DESIGN AND METHODS: We evaluated 107 cases of CHL for BCL6, CD79a, MUM1/IRF4 and B-cell transcription factors BOB.1, OCT.2 expression by immunohistochemistry. Statistical analysis was performed using Fisher's exact test, the Mann-Whitney test, the Kaplan-Meier method and the log rank test. Univariate and multivariate regression analyses were performed to identify variables with a significant effect on survival. RESULTS: CD79a was expressed in 5.8%, BCL6 in 14.7%, MUM1/IRF4 in 92.3%, BOB.1 in 53.4% and OCT.2 in 12.6% of cases. There was no significant association between CD79a or BCL6 expression and clinical characteristics. Univariate analysis showed that age of 45 or more, stage III and IV disease and MUM/IRF4 negative status were associated with significantly shorter time to progression (TTP) and overall survival (OS). On multivariate analysis the lack of MUM/IRF4 expression was associated with significantly shorter TTP while age of 45 or more and the presence of extralymphatic sites of disease were associated with significantly shorter OS. INTERPRETATION AND CONCLUSIONS: Our study has confirmed that MUM1/IRF4 is expressed in most cases of CHL and shows that lack of this expression in a minority of cases may be a potential adverse prognostic factor.

Disseminated intravascular B-cell lymphoma: clinicopathological features and outcome of three cases treated with anthracycline-based immunochemotherapy.

The purpose of this study was to evaluate the use of combination anthracycline-based immunochemotherapy in intravascular lymphoma (IVL). This is an extremely rare, disseminated, and aggressive extranodal CD20(+) non-Hodgkin's lymphoma (NHL) with poor outcome following anthracycline-based chemotherapy. From a population of 700 newly diagnosed patients with NHL who were registered and followed up at our unit between 1990 and 2005, three cases (0.4%) have been classified as IVL. Among the patients, there were two men and one woman, with a median age of 52 years. We have assessed the clinicopathological characteristics, response to therapy, and outcome. All patients presented with systemic symptoms and disseminated disease. All patients received anthracycline-based chemotherapy in combination with the anti-CD20 monoclonal antibody rituximab (immunochemotherapy). Complete remission was achieved in all three patients, and currently all remain progression free with a follow-up of 24-45 months. In conclusion, anthracycline-based immunochemotherapy induces durable remissions in patients with IVL, an ultimately fatal disease, suggesting that the clinical course of this disease may be altered with immunochemotherapy.

Blastic natural killer (NK)-cell lymphoma: report of an unusual CD4 negative case and review of the CD4 negative neoplasms with blastic features in the literature.

Blastic Natural Killer (NK)-cell lymphoma is a relatively new entity which has been recently included in the WHO classification. CD4 expression is observed in most cases of blastic NK-cell lymphomas and has been related with skin tropism. We report an unusual CD4 negative blastic NK-cell lymphoma with primary presentation in the skin, subsequent infiltration of the bone marrow and aggressive behavior. It is emphasized that extensive immunophenotyping and EBER RNA in situ hybridization are required in order to establish the diagnosis of blastic NK-cell lymphoma. We also present a review of the literature with respect to the CD4 negative NK-cell lymphomas with blastic morphological features.