Immunophenotyping of leukemia

Modern immunophenotyping of hematological malignancies by flow cytometry is assisted by a wide array of easily accessible monoclonal antibodies, by antibodies conjugated to diverse fluorochromes, and by reliable techniques for cell membrane permeabilization. Simultaneous assessment of multiple surface and intracellular markers at diagnosis reduces the number of cells required, helps the identification of the malignant cells and determines the degree of immunophenotypic heterogeneity of the malignant cell population. A few critical markers are sufficient to establish the lineage association in the majority of cases of acute and chronic leukemias and lymphomas. More extensive immunophenotyping can provide information about the cells' stage of differentiation, assess the expression of prognostically important features, and determine clonality. The identification of leukemia-associated immunophenotypes can be used for monitoring minimal residual disease during therapy. The presence of cells expressing these phenotypes in patients who are in clinical remission is associated with an increased risk of relapse.     

Minimax two-stage-designs with applications to tissue banking case-control studies

'Tissue banks' are created, at least in part, to help medical scientists learn about disease biology on the basis of samples provided by patients on treatment protocols that were competed years earlier.The bank inventory consists of precious non-renewable patient material (such as frozen diagnostic blood or bone marrow), which can be linked to both clinical data and long term follow-up information. Case-control studies, where cases represent clinical failures and controls clinical successes, are ideal for rapidly learning if a laboratory marker might have prognostic significance. While group sequential (multi-stage) methods are widely used in clinical trials, they have rarely been applied in case-control studies. Further, unlike clinical trials where safety and efficiency may actually be in conflict, case-control studies can focus on efficiency. Hence, minimizing the expected sample size is a desirable goal in such a setting. Since the true effect size is never known, and since no prior distribution can be postulated for the effect size, we have opted for the minimax solution. A strategy is developed to determine amongst all two-stage designs with given type I and type II errors, the one for which the maximum expected sample size is minimized. The user is provided with simple tables, whereby one can determine everything necessary to conduct the study from the corresponding calculation for a single-stage design. A matched pair example is given where the suggested design can be modified, to obtain a superior 'two-plus' stage design. The basic idea is to conduct the first stage as planned, but use the estimate of variance to redesign the study, without using the estimate of effect size in the redesign.     

Two novel mutations in mitochondrial acetoacetyl-CoA thiolase deficiency

Summary We report a new patient with acetoacetyl-CoA thiolase deficiency in whom we found two new missense mutations.     

Urotensin-II: a novel systemic hypertensive factor in the cat

Urotensin-II, a potent mammalian vasoconstrictor, may play a role in the etiology of essential hypertension. However, a species suitable for assessing such a role, one where a classical systemic hypertensive response (increase in mean blood pressure and systemic vascular resistance) is observed following bolus i.v. urotensin-II administration, has yet to be identified. The present study demonstrates that the cat may represent such a species since urotensin-II potently (pEC₅₀s 9.68±0.24–8.73±0.08) and efficaciously (E_max 73±15%–205±21% KCl) constricts all feline isolated arteries studied (aortae, renal, femoral, carotid, and mesenteric conduit/resistance). Accordingly, exogenous urotensin-II (1 nmol/kg, i.v.) effectively doubles both mean blood pressure (from 99±14 to 183±15 mmHg) and systemic vascular resistance (from 0.36±0.12 to 0.86±0.20 mmHg/ml/min) in the anaesthetized cat (without altering heart rate or stroke volume). Thus, in view of these profound contractile effects, the cat could be suitable for determining the effects of urotensin-II receptor antagonism on cardiovascular homeostasis in both normal and diseased states.     

Cytokine and vaccine therapy of kidney cancer

In this paper, results from current randomized and other relevant studies on cytokine and vaccine therapy of kidney cancer in the adjuvant setting and in metastatic disease are reviewed. Improvement of medical therapy of kidney cancer is required since the relative 5-year survival of kidney cancer is only 62%. In the adjuvant setting, cytokine monotherapy (interferon [IFN]-alpha or interleukin [IL]-2) is not effective in improving progression-free or overall survival. Recently, an autologous kidney cancer cell vaccine has been shown to reduce the risk of tumor progression following radical nephrectomy for organ-confined or locally advanced kidney cancer in a randomized Phase III study. There were only a few vaccine-related side effects. Presently, this is the only promising approach for the adjuvant treatment of kidney cancer following nephrectomy. In metastatic kidney cancer patients with the tumor-bearing kidney in situ, a combination of radical nephrectomy plus IFN-alpha is more effective than IFN-alpha alone. In metastatic kidney cancer without the option of operative removal of the primary tumor and/or metastases, cytokines such as IFN-alpha, IL-2 and IL-12 and their combinations result in response rates of 10-30%, but the 5-year overall survival is less than 10%. Furthermore, the ideal dose, administration and combination of different agents are yet to be defined. Vaccine therapy of metastatic kidney cancer has been investigated only in Phase I and II studies with limited clinical benefit. Based on the current literature there is a clear need for new approaches in metastatic kidney cancer.     

Interventional radiology techniques for the diagnosis of lymphoma or leukemia

BACKGROUND: Fluid aspiration, percutaneous biopsy, and catheter drainage are standard minimally invasive methods of diagnosing lymphoma or leukemia in adults. OBJECTIVE: To determine the effectiveness of interventional radiologic techniques in diagnosing specific hematologic malignancies in children. METHODS: During a 4-year period, 22 patients (16 male, 6 female; median age, 13 years) underwent 25 percutaneous biopsies, 6 fluid aspirations, 3 catheter drainages, and 1 needle localization for diagnosing suspected hematologic malignancy. RESULTS: For Hodgkin's disease, the procedures yielded 6 true-positive (TP) results, 2 true-negative (TN) results, and 2 false-negative (FN) results; for non-Hodgkin lymphoma (NHL), 14 TP results, 1 TN result, and 3 FN results; and for leukemia, 4 TP results and 3 FN results. Percutaneous biopsies yielded 16 TP results, 3 TN results, and 6 FN results. Aspirations and drainages yielded 8 TP results and 1 FN result. The one needle localization yielded a FN result. Overall sensitivity was 75%+/-7.3%; specificity, 100%; and accuracy, 77%+/-7.1%. CONCLUSION: Percutaneous biopsy of lymphoma is usually diagnostic. Drainage or aspiration of a fluid collection associated with NHL or leukemia is often diagnostic and is less invasive than biopsy. These procedures are minimally invasive and effective for diagnosing pediatric hematologic malignancies.