Myeloid neoplasm with t(3;8)(q26;q24): report of six cases and review of the literature.

Balanced translocation between chromosomes 3q26 and 8q24 is a very rare event. Here we report six patients with t(3;8)(q26;q24) either as a sole or as a part of genetic abnormalities. Five of the six patients were men with ages ranging from 41 to 84 years old. One patient had a long history of granulocyte colony stimulating factor (G-CSF) treatment. Three of the patients were initially diagnosed with acute myeloid leukemia, two with myelodysplastic syndrome and one with chronic myelogenous leukemia with blast crisis. The peripheral blood in all patients showed severe to moderate anemia; one had absolute neutropenia, one with neutrophilia; four had thrombocytopenia, two with thrombocytosis. The bone marrows from all patients showed dysmegakaryopoiesis with additional erythroid (three patients) and granulocytic (two patients) dysplasia. Cytogenetics revealed t(3;8)(q26;q24) as the sole abnormality in three patients. The majority of patients (4/6) had a poor clinical course, with an average survival of 10 months.

FASN and CD36 predict survival in rituximab-treated diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma is the most common lymphoid malignancy, as it accounts for approximately one third of all patient cases of non-Hodgkin's lymphoma. Patients with diffuse large B-cell lymphoma have markedly different treatment outcomes, suggesting a need for reliable prognostic factors and novel therapeutic approaches. De novo fatty acid synthesis is an important metabolic driver of tumor in multiple malignancies. In this retrospective study, we analyzed expression of fatty acid synthase (a key enzyme in de novo fatty acid synthesis), Spot 14 (thyroid hormone responsive Spot 14, a nuclear protein that promotes expression of genes involved in fatty acid synthesis), and CD36 (the cell surface channel for exogenous fatty acid uptake) in patients with diffuse large B-cell lymphoma and their clinical significance. We observed that overexpression of fatty acid synthase is negatively associated with overall survival (p=0.001) and progression-free period (p=0.004) in patients with diffuse large B-cell lymphoma. Multivariate analysis showed that fatty acid synthase overexpression is an independent prognostic marker of aggressive clinical course. For the first time, we report CD36 as an independent protective factor in patients treated with rituximab. Thus, fatty acid synthase and CD36 expression may serve as prognostic markers to predict response to treatment and survival in diffuse large B-cell lymphoma patients. Fatty acid synthase may also be a potential therapeutic target in lymphoid malignancies.

Chromosomal instability substantiates poor prognosis in patients with diffuse large B-cell lymphoma.

PURPOSE: The specific role of chromosomal instability (CIN) in tumorigenesis has been a matter of conjecture. In part, this is due to the challenge of directly observing chromosome mis-segregation events as well as the inability to distinguish the role of CIN, which consists of increased rates of chromosome mis-segregation, from that of aneuploidy, which is a state of nondiploid chromosome number. EXPERIMENTAL DESIGN: Here, we examine the contribution of CIN to the prognosis of patients diagnosed with diffuse large B-cell lymphoma (DLBCL) by directly surveying tumor cells, fixed while undergoing anaphase, for evidence of chromosome mis-segregation. Hematoxylin and eosin-stained samples from a cohort of 54 patients were used to examine the relationship between frequencies of chromosome mis-segregation and patient prognosis, overall survival, and response to treatment. RESULTS: We show that a two-fold increase in the frequency of chromosome mis-segregation led to a 24% decrease in overall survival and 48% decrease in relapse-free survival after treatment. The HR of death in patients with increased chromosome mis-segregation was 2.31 and these patients were more likely to present with higher tumor stage, exhibit tumor bone marrow involvement, and receive a higher International Prognostic Index score. CONCLUSIONS: Increased rates of chromosome mis-segregation in DLBCL substantiate inferior outcome and poor prognosis. This is likely due to increased heterogeneity of tumor cells leading to a larger predilection for adaptation in response to external pressures such as metastasis and drug treatments. We propose that targeting CIN would yield superior prognosis and improved response to chemotherapeutic drugs.

What is psychonephrology?

Patients on forms of dialysis and those who receive kidney transplants face many stresses connected with their illness and forms of treatment. These stresses may result in a variety of psychiatric disorders and other problems. It is the duty of all nephrology personnel to be aware of these problems, and inquire about them so that the appropriate treatment may be instituted. The major stresses of dialysis involve conflicts of dependency and independency, unrealistic expectations, the medical regimen and the many losses these patients sustain. As a consequence of these stresses and other factors, patients experience depression, anxiety, sexual problems, psychosis, problems in rehabilitation and uncooperativeness. The therapies of these disorders include individual and group therapy and the use of psychologically active medications. The pharmacokinetics of medications used to treat these patients require special consideration of the route of elimination, whether or not the medication is dialyzable and the protein binding of the medicine. Renal transplant patients may experience the same psychiatric problems, but usually of a lesser degree. Their special stress is termed "The Sword of Damocles'" that refers to anxiety associated with the wait and worry of organ rejection.

Peripheral T-cell lymphoma presenting as sclerouveitis.

PURPOSE: To report an unusual case of ocular peripheral T-cell lymphoma presenting as sclerouveitis. METHODS: A 53-year-old woman presented with painful, unilateral sclerouveitis and was initially treated with antivirals and corticosteroids for what was presumed to be isolated ocular HSV infection with vasculitis. When she failed to improve the conjunctiva was biopsied and characterized by immunohistochemical and molecular methods. The literature regarding conjunctival T-cell lymphomas as well as lymphomas mimicking scleritis is reviewed. RESULTS: Biopsies of a scleral/conjunctival nodule from the right eye were obtained on 2 occasions, the second of which revealed the presence of intermediate to large size lymphocytes that were CD3, T-cell intracellular antigen 1 and Granzyme B positive but CD56 and Epstein Barr virus negative. Polymerase chain reaction showed clonal T-cell receptor gamma rearrangements in DNA samples isolated from biopsy tissue. Another biopsy was obtained from a mucosal lesion in the oropharynx, which was shown to contain an identical T-cell receptor gamma rearrangement. These results led to the diagnosis of peripheral T-cell lymphoma. Conjunctival T-cell lymphomas have been reported in two other patients both of which also had involvement of upper airway structures. Five other reports of lymphoma mimicking scleritis are discussed. CONCLUSIONS: Peripheral T-cell lymphoma should be considered in the differential diagnosis of patients who present with sclerouveitis of unknown etiology unresponsive to conventional therapy. If a conjunctival T-cell lymphoma is identified a systemic evaluation for lymphoma with particular attention to the upper airway is justified.

Quantitative assessment of the BCR-ABL transcript using the Cepheid Xpert BCR-ABL Monitor assay.

CONTEXT: Chronic myelogenous leukemia (CML) and the assessment of the BCR-ABL transcript has become a new paradigm. Novel tyrosine kinase inhibitors as mainstream therapeutic options for the CML patient warrant routine quantification of the BCR-ABL transcript. The Xpert BCR-ABL Monitor assay is a nested reverse transcriptase polymerase chain reaction that greatly reduces technical time by using a single cartridge to isolate RNA and run a quantitative reverse transcriptase polymerase chain reaction. OBJECTIVE: To evaluate the Xpert BCR-ABL Monitor assay for quantitative assessment of the BCR-ABL transcript in CML patients. DESIGN: A standard curve of K-562 cells diluted in normal peripheral blood was used to test the sensitivity, linearity, and percent coefficient of variation of the assay. Specimen stability was tested by running standard curves immediately and after 24 hours or 96 hours of storage at 4 degrees C. Specimens from normal controls, patients known to have CML, or patients suspected of having CML were also tested. RESULTS: The sensitivity of the assay was sufficient to detect 1 K-562 cell in 10(5) normal cells. The R2 of the standard curve was 0.98 and the percent coefficient of variation for each data point was 15% to 24%. Eleven of 14 patients with known CML on imatinib treatment tested positive for the BCR-ABL transcript, whereas 10 normal controls tested negative. CONCLUSIONS: The Xpert BCR-ABL Monitor assay is a rapid, sensitive method for monitoring the presence of the BCR-ABL transcript in CML patients. The single-use cartridge minimizes hands-on technical time, minimizes the potential for contamination, and allows quantitative BCR-ABL testing to be performed in a random access fashion.

Update on psychotropic medication use in renal disease.

Renal failure is a common medical condition, and many patients have comorbid psychiatric disorders. In this review, which is intended as a resource for consultation psychiatrists, the authors discuss pharmacokinetic considerations and provide information about the use of individual psychotropic medications in patients with renal disease. Most psychotropic medications are fat soluble, easily pass the blood-brain barrier, are not dialyzable, are metabolized primarily by the liver, and are excreted mainly in bile. Consequently, the majority of these drugs can be safely used with the end-stage renal disease population.