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Biomedical subjects

Marcel P Devetten

Publications and source records attributed to Marcel P Devetten.

7 recordsLinked to original sources

Bulky lymphadenopathy with poor clinical outcome is associated with ATM downregulation in B-cell chronic lymphocytic leukemia patients irrespective of 11q23 deletion.

B-cell chronic lymphocytic leukemia (B-CLL) is the most common B-cell leukemia among older populations in Western countries. The clinical course of B-CLL is heterogeneous: in some patients the disease course is indolent, in others it is aggressive. The B-CLL subgroups with chromosome 11q23 deletion have been associated with aggressive disease course involving ATM deletion, extensive bulky lymphadenopathy (BLA), and inferior clinical outcome. Using real-time reverse transcriptase-polymerase chain reaction, we found that ATM was consistently underexpressed in B-CLL patients with BLA, irrespective of 11q23 deletion status. In addition, B-CLL patients who presented with BLA had a significantly shorter time to treatment (2 months) than did patients without BLA (74 months). Moreover, gene expression analysis in B-CLL patients with and without BLA revealed differences in expression for genes involved in apoptosis, cell cycle, and cell adhesion. These results indicate an association between BLA and reduced expression of ATM, suggesting a role for ATM in disease progression in B-CLL.

Ataxia Telangiectasia Mutated Proteins↗

Use of interferon-alpha in patients with West Nile encephalitis: report of 2 cases.

We describe 2 patients with West Nile virus (WNV) encephalitis who were treated experimentally with interferon (IFN)-alpha. Both patients demonstrated substantial improvement in mentation and speech on the second day of experimental therapy, and neither required endotracheal intubation or admission to the intensive care unit during hospitalization. Moreover, during the 9-month follow-up period, one patient achieved complete recovery, and the other nearly achieved complete resolution of sequelae. To our knowledge, this is the first published report of the use of IFN-alpha to treat WNV encephalitis. Clinical trials are underway to further define the role of this therapy in persons with WNV encephalitis.

Adult↗

Graft-versus-host disease: how to translate new insights into new therapeutic strategies.

Graft-versus-host disease occurs when transplanted donor-derived T lymphocytes recognize major or minor histocompatibility complex proteins and their associated peptides expressed by recipient antigen-presenting cells. A widely accepted paradigm for the pathophysiology of acute GVHD is based on the existence of 3 sequential steps: (1) injury to the host environment (as would occur during conditioning regimens); (2) donor T-cell activation, proliferation, and differentiation; and (3) damage to the target tissue caused by either cytotoxicity or indirectly by inflammatory cytokines. In order to reduce the incidence of GVHD, recent studies have focused on methods of prophylaxis as well as novel treatments for established GVHD. We review each phase in the development of acute GVHD and discuss recently developed interventions aimed to prevent or treat GVHD by interfering with these pathways.

Bone Marrow Transplantation↗

Utility of a prognostic scoring system for allogeneic stem cell transplantation in patients with chronic myeloid leukemia.

Allogeneic stem cell transplantation (SCT) is the treatment of choice for selected patients with chronic myeloid leukemia (CML). However, it is associated with a high risk of treatment-related mortality (TRM) and morbidity. To assist in decision making about transplantation, a simple scoring system to assess the risk is needed. We analyzed the utility of a scoring system, first reported by the European Group for Blood and Marrow Transplantation (EBMT). We analyzed the data from 31 patients who underwent allogeneic transplantation at our institution, using the EBMT scoring system. It was based on five pretransplant risk factors: donor type, stage of disease at time of transplantation, age of recipient, sex of donor and recipient, and interval between diagnosis and transplant. Seventeen patients had a risk score of 0-2, and 14 patients had a score of 3-7. Using Kaplan-Meier analysis, the estimated 4-year leukemia-free (LFS) and overall survival (OS) for patients with a score of 0-2 were 47 and 53%, respectively. In contrast, the estimated 4-year LFS and OS for patients with a score of 3-7 were 10.5 and 10.5%, respectively. Four-year TRM was 47% for the low-risk group (0-2), and 85% for the high-risk group (3- 7). This simple scoring system may play an important role in predicting the outcome of allogeneic SCT, and in choosing the appropriate therapy for patients with CML.

Adult↗

High-dose therapy and autologous stem cell transplantation in relapsed and refractory Hodgkin's disease: outcome based on a prognostic model.

We evaluated the results of high-dose therapy (HDT) and autologous hematopoietic stem cell transplantation (ASCT) in patients with relapsed or primary refractory Hodgkin's disease (HD), using a previously reported prognostic model based on the presence of three poor prognostic factors at the start of salvage therapy/preparative regimen: B symptoms, extranodal disease and the duration of last complete response of less than 1 year. Based on this model, the patients were divided into low-risk and high-risk groups. Between 1993 and 2001, 24 patients with HD were treated with HDT and ASCT. Eighteen of the 24 patients had 0-1 risk factors (low-risk group) and 6 patients had 2-3 risk factors (high-risk group). Using Kaplan-Meier analysis, after a median follow-up of 40.5 months, the progression-free survival (PFS) was 48%, and the overall survival (OS) was 55%. PFS in the low-risk group was 56%, and in the high-risk group 17% (p < 0.001). OS in the low-risk group was 68% and in the high-risk group it was 18% (p < 0.001). The 100-day transplant-related mortality for the entire group was 16%. Our results are comparable to those reported in previous clinical trials for patients with refractory and relapsed HD treated with HDT and ASCT. The use of a prognostic model appears useful for predicting the outcome of HDT and ASCT for HD patients, and may play an important role in choosing the appropriate therapy for these patients.

Adolescent↗