Leukemia & lymphoma
-
Leukemia & lymphoma · Jan 2011
A potential mechanism of rituximab-induced inhibition of tumor growth through its sensitization to tumor necrosis factor-related apoptosis-inducing ligand-expressing host cytotoxic cells.
Rituximab (anti-CD20 mAb) mediates antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and apoptosis in B-NHL cells. The contribution of other host-mediated cytotoxic effects has not been examined. The expression of death-inducing ligands (e.g. ⋯ Rituximab-mediated sensitization to TRAIL apoptosis was due, in large part, to rituximab-mediated inhibition of the transcription factor Yin Yang 1 (YY1). The direct role of YY1 in TRAIL sensitization by rituximab was shown in cells transfected with YY1 siRNA, and such cells mimicked rituximab and became sensitive to TRAIL-induced apoptosis. These data suggest that, in vivo, host effector cells expressing TRAIL may contribute to rituximab-mediated depletion of B-NHL cells.
-
Leukemia & lymphoma · Dec 2010
Phase I study of dose-escalated busulfan with fludarabine and alemtuzumab as conditioning for allogeneic hematopoietic stem cell transplant: reduced clearance at high doses and occurrence of late sinusoidal obstruction syndrome/veno-occlusive disease.
Disease recurrence after allogeneic hematopoietic cell transplant (alloHCT) remains common, making improvements in conditioning regimens desirable. A dose-response relationship between busulfan exposure and outcome is known. Using individual real-time monitoring of the busulfan area under the curve (AUC), we aimed to determine the maximum-tolerated busulfan AUC in a conditioning regimen with fludarabine/alemtuzumab. ⋯ The risk for SOS/VOD correlated with the highest observed AUC (AUC(max)) rather than with the average cumulative AUC (AUC(avg)). Busulfan dose-escalation to a maximum-tolerated AUC of 5800 µmol-min/L-higher than that achieved by current standard busulfan regimens-was accurate and achievable using real-time pharmacokinetics monitoring of the first conditioning dose. This AUC is now being studied in phase II for patients receiving busulfan/fludarabine/alemtuzumab as alloHCT conditioning.
-
Patients with hematologic disease are likely to be at increased risk for infection with influenza. We retrospectively analyzed 11 cases of patients with hematologic disease who were infected with pandemic H1N1 virus in our department, including their clinical manifestations, laboratory and imaging findings, outcomes of antiviral therapy, and factors associated with mortality. ⋯ Five patients progressed to respiratory failure and eventually died, despite treatment with antivirals and/or corticosteroids and/or mechanical ventilation. We concluded that H1N1 2009 infection was associated with a severe course and high rate of mortality in patients with hematologic disease, and early diagnosis and antiviral treatment were important to reduce the rate of severe complications and mortality.
-
Leukemia & lymphoma · Sep 2010
ReviewApproaches to the early treatment of invasive fungal infection.
Invasive fungal infections account for significant morbidity and mortality in the seriously immunocompromised host, especially those suffering from hematologic malignancies and the recipients of hematopoietic cell transplant. One of the reasons for the continuing high mortality rates due to invasive fungal infection is the delay in administering appropriate therapy. ⋯ Here, we present our approach to both invasive candidiasis and invasive mold infection. Therapy should be initiated at the first signs and symptoms of disease, utilizing knowledge of local fungal epidemiology, the patient's recent antifungal agent exposure, and the diagnostic tests immediately available, to select an appropriate antifungal agent most likely to be effective against the suspected fungal species.