In patients with invasive aspergillosis, initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B.

Infection with the human immunodeficiency virus type 1 (HIV-1) requires the presence of a CD4 receptor and a chemokine receptor, principally chemokine receptor 5 (CCR5). Homozygosity for a 32-bp deletion in the CCR5 allele provides resistance against HIV-1 acquisition. We transplanted stem cells from a donor who was homozygous for CCR5 delta32 in a patient with acute myeloid leukemia and HIV-1 infection. The patient remained without viral rebound 20 months after transplantation and discontinuation of antiretroviral therapy. This outcome demonstrates the critical role CCR5 plays in maintaining HIV-1 infection.

Standardized guidelines for the baseline evaluation and response assessment of primary CNS lymphoma (PCNSL) are critical to ensure comparability among clinical trials for newly diagnosed patients. The relative rarity of this tumor precludes rapid completion of large-scale phase III trials and, therefore, our reliance on the results of well-designed phase II trials is critical. To formulate this recommendation, an international group of experts representing hematologic oncology, medical oncology, neuro-oncology, neurology, radiation oncology, neurosurgery, and ophthalmology met to review current standards of reporting and to formulate a consensus opinion regarding minimum baseline evaluation and common standards for assessing response to therapy. The response guidelines were based on the results of neuroimaging, corticosteroid use, ophthalmologic examination, and CSF cytology. A critical issue that requires additional study is the optimal method to assess the neurocognitive impact of therapy and address the quality of life of PCNSL survivors. We hope that these guidelines will improve communication among investigators and comparability among clinical trials in a way that will allow us to develop better therapies for patients.

HIV entry into CD4 ؉ cells requires interaction with a cellular receptor, generally either CCR5 or CXCR4. We have previously reported the case of an HIV-infected patient in whom viral replication remained absent despite discontinuation of antiretroviral therapy after transplantation with CCR5⌬32/⌬32 stem cells. However, it was expected that the long-lived viral reservoir would lead to HIV rebound and disease progression during the process of immune reconstitution. In the present study, we demonstrate successful reconstitution of CD4 ؉ T cells at the systemic level as well as in the gut mucosal immune system after CCR5⌬32/⌬32 stem cell transplantation, while the patient remains without any sign of HIV infection. This was observed although recovered CD4 ؉ T cells contain a high proportion of activated memory CD4 ؉ T cells, ie, the preferential targets of HIV, and are suscep- IntroductionDestruction of the immune system by the HIV is driven by the loss of CD4 ϩ T cells in the peripheral blood and lymphoid tissues. Viral entry into CD4 ϩ cells is mediated by the interaction with a cellular chemokine receptor, the most common of which are CCR5 and CXCR4. 1 Because subsequent viral replication requires cellular gene expression processes, activated CD4 ϩ cells are the primary targets of productive HIV infection. Consequently, HIV infection leads predominantly to the depletion of activated memory CD4 ϩ T cells, most of which reside in the gastrointestinal (GI) mucosa. [2][3][4] Although therapeutic control of HIV replication allows the immune system to partially restore and delays disease progression, the cure of HIV infection remains still unachievable with use of the currently available antiretroviral drugs. The major barrier to viral eradication in patients receiving antiretroviral therapy (ART) is the establishment of HIV reservoirs, including low-level productively and latently infected cells. [5][6][7] Thus, maintenance of replicationcompetent HIV in long-lived cells and distinct anatomical sanctuaries allows the virus to reseed the body once ART is discontinued. 8 Cells of persons homozygous for the CCR5 gene variant ⌬32 (CCR5⌬32/⌬32) are naturally resistant to infection with CCR5-tropic HIV strains (R5 HIV) because of the lack of CCR5 cell-surface expression. 9 Previously, we demonstrated the feasibility of hematopoietic stem cell transplantation (SCT) with CCR5⌬32/ ⌬32 donor cells (CCR5⌬32/⌬32 SCT) in an HIV-infected patient with relapsed acute myeloid leukemia (AML) and documented absent viremia during the first 20 months of remission, during which time the patient did not receive ART. 10,11 This case clearly emphasizes the importance for continuing research in the field of CCR5-targeted treatment strategies, but uncertainty has remained over whether a cure for HIV infection has been achieved in this patient.In the setting of HIV infection, the effects of pretransplantation conditioning do not allow the complete elimination of HIV, as demonstrated by previous studies in which researchers demonstrated that HIV...

Background: High-dose methotrexate (HDMTX) is considered standard of care for

A monocytic cell line, termed Mono Mac, was established from peripheral blood of a patient with monoblastic leukemia. Two clones, designated Mono Mac I and Mono Mac 6, were isolated and both were assigned to the monocyte lineage on the basis of morphological, cytochemical and immunological criteria. Most importantly, the clones express NaF-sensitive non-specific-esterase, produce reactive oxygen and stain with MAb My4. Mono Mac 6, in addition, constitutively exhibits phagocytosis of antibody-coated erythrocytes in 80% of the cells and reacts with a panel of MAbs that are specific for mature monocytes, i.e., M42, LeuM3, 63D3, Mo2 and UCHMI. By contrast, the monoblastic cell lines U937 and THP-I are negative for all these markers. Only expression of My4 could be detected after differentiation induced by interferon-gamma (IFN-gamma). Similar treatment of Mono Mac I, however, resulted in staining with all the monocyte-specific MAbs mentioned above, while IFN-gamma treatment of Mono Mac 6 enhanced antigen expression. In addition, the cells showed an increased frequency of multinucleated cells with a rise from 4.8% to 21.9%. Mono Mac 6 appears to be the only one of the cell lines studied to constitutively express phenotypic and functional features of mature monocytes.

Adult patients with acute lymphoblastic leukemia (ALL) who are stratified into the standard-risk (SR) group due to the absence of adverse prognostic factors relapse in 40% to 55% of the cases. To identify complementary markers suitable for further treatment stratification in SR ALL, we evaluated the predictive value of minimal residual disease (MRD) and prospectively monitored MRD in 196 strictly defined SR ALL patients at up to 9 time points in the first year of treatment by quantitative polymerase chain reaction (PCR). Frequency of MRD positivity decreased from 88% during early induction to 13% at week 52. MRD was predictive for relapse at various follow-up time points. Combined MRD information from different time points allowed definition of 3 risk groups (P < .001): 10% of patients with a rapid MRD decline to lower than 10 ؊4 or below detection limit at day 11 and day 24 were classified as low risk and had a 3-year relapse rate (RR) of 0%. A subset of 23% with an MRD of 10 ؊4 or higher until week 16 formed the high-risk group, with a 3-year RR of 94% (95% confidence interval [CI] 83%-100%). The remaining patients whose RR was 47% (31%- 63% IntroductionInvestigation of minimal residual disease (MRD) has been proven to be a valuable tool for predicting outcome in childhood acute lymphoblastic leukemia (ALL). [1][2][3][4][5] In contrast, only a few studies have focused on adult ALL, and they were based mostly on patients with heterogeneous risk profiles and different kinds and intensities of treatment. [6][7][8] However, monitoring homogeneous patient cohorts at different time points during therapy might provide additional insight into the nature and clinical relevance of MRD kinetics in adult ALL, which is particularly relevant for the large population of standard-risk (SR) patients without conventional risk factors. Relapses in this patient group occur in about 40% to 55% of cases and cannot be predicted by any known conventional risk factor. [9][10][11] In a number of clinical studies this led to a policy of stem cell transplantation (SCT) in first remission, 12-14 causing overtreatment and additional expenses for those patients who are cured by conventional chemotherapy alone. Therefore, definition of prognostic factors allowing discrimination of SR patients with poor outcome after standard chemotherapy from those with a favorable prognosis is highly warranted. Currently, the most widely used techniques to detect and quantify residual disease in patients with ALL are multiparameter immunophenotypic evaluation of aberrant protein expression 2,3,8 and clone-specific polymerase chain reaction (PCR) amplification of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements. 1,4,5 Such molecular targets can be identified in more than 90% of patients with ALL by the use of various PCR primer sets. Besides its large applicability and high sensitivity, a main advantage of PCR-based assays is the use of DNA as a stable and easy conveyable specimen, which is particularly relevant in large multicenter studies....

Quantification of minimal residual disease (MRD) by real-time PCR directed to