Mutations in the human telomerase RNA (TERC) occur in autosomal dominant dyskeratosis congenita (DKC). Because of the possibility that TERC mutations might underlie seemingly acquired forms of bone marrow failure, we examined blood samples from a large number of patients with aplastic anemia (AA), paroxysmal nocturnal hemoglobinuria (PNH), and myelodysplasia (MDS).

A serious complication of aplastic anemia (AA) is its evolution to clonal hematologic diseases such as myelodysplasia (MDS) and leukemia, which is usually associated with the appearance of a cytogenetic abnormality in bone marrow cells. We present here an analysis of a cohort of 30 patients with otherwise typical AA in whom clonal karyotypic evolution was observed during frequent periodic marrow examinations. The actuarial risk for this complication has been estimated in other studies at around 15% at 5 years. Conversion from normal to abnormal karyotype occurred at a constant rate after initial diagnosis, with about 50% of cases developing within the first 30 months. Transient chromosomal abnormalities were infrequent. Clinically, AA patients with clonal cytogenetic patterns were heterogenous; a variety of karyotypic defects with numerical and structural abnormalities of chromosome 7 accounted for 40% of all cases followed by trisomy 8, structural and numerical abnor-

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IST produced significant improvement in the pancytopenia of a substantial proportion of patients with MDS and was associated with improved overall and progression-free survival, especially in younger individuals with lower-risk disease.

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Context Critically short telomeres produce apoptosis, cell senescence, and chromosomal instability in tissue culture and animal models. Variations in telomere length have been reported in severe aplastic anemia but their clinical significance is unknown.Objective To investigate the relationship between telomere length and clinical outcomes in severe aplastic anemia. Design, Setting, and Patients Single institution analysis of 183 patients with severe aplastic anemia who were treated in sequential prospective protocols at the National Institutes of Health from 2000 to 2008. The pretreatment leukocyte ageadjusted telomere length of patients with severe aplastic anemia consecutively enrolled in immunosuppression protocols with antithymocyte globulin plus cyclosporine for correlation with clinical outcomes were analyzed. Main Outcome Measures Hematologic response, relapse, clonal evolution, and survival. ResultsThere was no relationship between hematologic response and telomere length with response rates of 56.5% of 46 patients in the first, 54.3% of 46 in the second, 60% of 45 in the third, and 56.5% of46 in the fourth quartiles. Multivariate analysis demonstrated that telomere length was associated with relapse, clonal evolution, and mortality. Evaluated as a continuous variable, telomere length inversely correlated with the probability of hematologic relapse (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.03-0.69; P=.01). The probability of clonal evolution was higher in patients in the first quartile (24.5%; 95% CI, 8.7%-37.5%) than in quartiles 2 through 4 (8.4%; 95% CI, 3.2%-13.3%; P=.009), and evolution to monosomy 7 or complex cytogenetics was more common in the first quartile (18.8%; 95% CI, 3.5%-31.6%) than in quartiles 2 through 4 (4.5%; 95% CI, 0.5%-8.2%; P = .002). Survival between these 2 groups differed, with 66% (95% CI, 52.9%-82.5%) surviving 6 years in the first quartile compared with 83.8% (95% CI, 77.3%-90.9%) in quartiles 2 through 4 (P=.008). ConclusionIn a cohort of patients with severe aplastic anemia receiving immunosuppressive therapy, telomere length was unrelated to response but was associated with risk of relapse, clonal evolution, and overall survival.

In 1995, the U.S. Public Health Service (USPHS) and the Infectious Diseases Society of America (IDSA) developed guidelines for preventing opportunistic infections (OIs) among persons infected with human immunodeficiency virus (HIV); these guidelines were updated in 1997 and 1999. This fourth edition of the guidelines, made available on the Internet in 2001, is intended for clinicians and other health-care providers who care for HIV-infected persons. The goal of these guidelines is to provide evidence-based guidelines for preventing OIs among HIV-infected adults and adolescents, including pregnant women, and HIV-exposed or infected children. Nineteen OIs, or groups of OIs, are addressed, and recommendations are included for preventing exposure to opportunistic pathogens, preventing first episodes of disease by chemoprophylaxis or vaccination (primary prophylaxis), and preventing disease recurrence (secondary prophylaxis). Major changes since the last edition of the guidelines include 1) updated recommendations for discontinuing primary and secondary OI prophylaxis among persons whose CD4+ T lymphocyte counts have increased in response to antiretroviral therapy; 2) emphasis on screening all HIV-infected persons for infection with hepatitis C virus; 3) new information regarding transmission of human herpesvirus 8 infection; 4) new information regarding drug interactions, chiefly related to rifamycins and antiretroviral drugs; and 5) revised recommendations for immunizing HIV-infected adults and adolescents and HIV-exposed or infected children.