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Anthony D Ho

Publications and source records attributed to Anthony D Ho.

76 records · Page 5Linked to original sources
PubMed2002

Dose-dependent effect of thalidomide on overall survival in relapsed multiple myeloma.

PURPOSE: Although thalidomide (Thal) was introduced successfully in the treatment of multiple myeloma (MM), the optimal Thal dosage and schedule are still controversial. The aim of this study was to analyze whether the effect of Thal in MM is dose dependent and whether the outcome might be improved when the Thal dosage is adjusted to parameters reflecting body size. EXPERIMENTAL DESIGN: From December 1998 to March 2001, 83 patients with relapsed MM were enrolled in a clinical Phase II trial and treated with a maximum Thal dosage of 400 mg daily. We performed a retrospective analysis and studied the effect of the cumulative 3-month Thal dosage on progression-free survival and overall survival (OS) together with age and the pretreatment levels of beta2-microglobulin, C-reactive protein, albumin, and hemoglobin in a Cox regression model. RESULTS: After a median follow-up time of 17 months (range, 1-30 months), the estimated 12-month progression-free survival and OS were 45% (SE = 6%) and 86% (SE = 4%) for the whole patient group. After backward selection, hemoglobin (P = 0.002) and the cumulative 3-month Thal dosage (P = 0.002) were the remaining factors for OS. The effect on OS could not be improved when the cumulative 3-month Thal dosage was adjusted to parameters reflecting body size such as height, weight, body surface area, or body mass index in comparison with Thal alone. CONCLUSIONS: Our retrospective analysis demonstrates that the cumulative 3-month Thal dosage is one of the major prognostic factors for OS, supporting the hypothesis of a dose-dependent effect of Thal in relapsed MM.

Adult↗
PubMedDate not supplied

Highly efficient expansion of human CD4+CD25+ regulatory T cells for cellular immunotherapy in patients with graft-versus-host disease.

CD4+CD25+ regulatory T cells (T(REG)) are engaged in the regulation of murine and human immune responses as well as graft-versus-host disease (GvHD) after allogeneic stem-cell transplantation. Despite their suppression of GvHD they do not impair graft-versus-tumor activity in the mouse, which makes T(REG) especially attractive candidates for cellular immunotherapy. T(REG) comprise only 5% to 10% of CD4+ T cells in peripheral blood and are naturally anergic, which prevented their use as therapeutic suppressor cells in the context of autoimmune or alloimmune reactions so far. We therefore developed an in vitro expansion protocol for human T(REG), breaking their anergy with anti-CD3/anti-CD28-coupled paramagnetic beads and a combination of interleukin (IL)-2 and IL-15. Highly purified human T(REG) can be expanded 285-fold to 1000-fold within 20 days and keep their phenotype as well as all their suppressor functions even in the context of stimulation with mature allogeneic dendritic cells. However, we demonstrate that FoxP3 is not a reliable marker for human T(REG) as it is transiently inducible in CD4+CD25- cells upon activation with cytokines or via their T cell receptor. In addition, we successfully expanded CD4+CD25+ cells from patients after allogeneic stem-cell transplantation with or without GvHD and show that different suppressor functions might be lost independently, demonstrating that human T(REG) biology is likely more complicated than previously thought.

Adult↗
PubMedDate not supplied

Psychiatric comorbidity and work disability in patients with inflammatory rheumatic diseases.

OBJECTIVE: To determine the relative contribution of psychiatric comorbidity to work disability in patients with inflammatory rheumatic diseases (IRD). Parallel analyses were also performed in a matched control group with no diagnosis of IRD to investigate if predictors of work disability in medical patients are independent from the presence of IRD. METHOD: The patient group with IRD (73.9% female; mean age, 42.7 years) and the control group (73.9% female; mean age, 42.2 years) consisted of 356 outpatients each. Psychiatric comorbidity was diagnosed using the Patient Health Questionnaire (PHQ), functional disability was measured with the 12-item Short-Form Health Survey (SF-12), and severity of illness was assessed by the treating physicians. Stepwise logistic regression analyses were performed to identify independent predictors of work disability controlling for psychiatric comorbidity, functional disability, severity of illness, additional clinical variables, and demographics. RESULTS: Psychiatric comorbidity increased work disability in patients with severe IRD from 25% to 50%, and from 5% to 17% in mild disease. Physical functioning (OR = 0.6; p <.0001), depression severity (OR = 1.6; p =.005), and illness severity (OR = 1.8; p =.006) were identified as independent predictors of work disability in patients with IRD. Similar predictors of work disability were identified in the control group, but depression severity did not meet statistical significance at the 5% level. CONCLUSIONS: This study provides evidence that depression is an independent risk factor of work disability in patients with IRD, but this result cannot be generalized to other medical conditions. Improved diagnosis and treatment of depressive disorders in patients with IRD may help avoid work disability.

Adult↗