0000000000672806
AUTHOR
G Derigs
Human interleukin-4 enhances stromal cell-dependent hematopoiesis: costimulation with stem cell factor
Abstract Interleukin-4 (IL-4) has distinct hematopoietic activities, primarily as a costimulant with other cytokines to enhance colony formation of hematopoietic progenitors. We investigated the influence of IL-4 on stromal cell-supported long-term cultures (LTCs) of normal human bone marrow. Addition of IL-4 to LTCs of unseparated bone marrow or highly enriched CD34+ cells resulted in a significant increase of myeloid progenitors in the nonadherent, as well as in the stromal cell-adherent cell populations. In contrast, the total cell number was not influenced by IL-4, suggesting a selective effect on primitive progenitor cells. Cord blood cells or CD34+ bone marrow cells were incubated wit…
Relapse risk after autologous transplantation in patients with newly diagnosed myeloma is not related with infused tumor cell load and the outcome is not improved by CD34+ cell selection: long term follow-up of an EBMT phase III randomized study.
BACKGROUND AND OBJECTIVES: This European Group for Blood and Marrow Transplantation (EBMT) multicentre randomized phase III study was designed to assess the safety and efficacy of CD34+ selection in newly diagnosed myeloma patients undergoing autologous transplantation. DESIGN AND METHODS: One hundred and eleven patients responsive to initial chemotherapy were randomized to receive CD34+ selected (arm A) or unselected PBPC (arm B) after conditioning with high-dose melphalan and TBI. ASO-PCR was used to assess purging efficacy and reinfused tumor load. Tumor load could be assessed in 59 patients. RESULTS: CD34+ selection gave a median tumor cell depletion of 2.2 logs (0.77-5.96). No tumor ce…
Regulation of cytokine expression by interferon-alpha in human bone marrow stromal cells: inhibition of hematopoietic growth factors and induction of interleukin-1 receptor antagonist
We investigated the effects of interferon-alpha (IFN-alpha) on the expression of cytokines by human bone marrow stromal cells. Production of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte-CSF (G-CSF), and interleukin-1 beta (IL-1 beta) in stromal cell layers was induced by incubation with IL-1 alpha, tumor necrosis factor (TNF), or lipopolysaccharide (LPS). Addition of IFN-alpha to such stimulated cultures resulted in a strong downregulation of mRNA expression of GM-CSF and IL-1 beta. Similarly, the protein levels of GM- CSF and IL-1 beta were significantly reduced by IFN-alpha, whereas G- CSF production was only moderately inhibited. In contrast, IFN-alpha markedly …
Efficacy of Rituximab Combined in Salvage- and High Dose-Therapy (HDT) for Patients with Relapsed NHL; Interim Analysis of a Multicenter Phase II Study.
Abstract The introduction of Rituximab (R) in the treatment of B-NHL resulted in improvement in first line therapies for indolent (ind.) and aggressive (agg.) B-NHL. However, the value of R in intensive chemotherapy relapse strategies has not definitely been demonstrated. In a phase I/II clinical trial we have demonstrated safety of R as an in vivo purging agens in salvage and high dose therapy for relapsed/refractory B-NHL. This led, with promising response rates, to the initiation of a multicenter phase II trial to further prove therapeutic efficacy. Inclusion criteria were: Pt < 65 years, ECOG < 3, relapse or progression for patients with ind. NHL and induction failure or relapse f…
Prognosis of patients with primary central nervous system lymphoma after high-dose chemotherapy followed by autologous stem cell transplantation
High-dose chemotherapy followed by autologous stem cell transplantation has been shown to be feasible and highly effective in newly diagnosed primary central nervous system lymphoma. In this retrospective multicenter study, we investigated prognosis and baseline risk factors in patients with primary central nervous system lymphoma who underwent this treatment approach. We retrospectively analyzed 105 immunocompetent patients with primary central nervous system lymphoma who underwent high-dose chemotherapy followed by autologous stem cell transplantation with or without whole brain radiotherapy as first-line consolidation treated at 12 German centers between 1997 and 2011. We estimated survi…