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1.
Transfusion ; 53(1): 76-84, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22624594

ABSTRACT

BACKGROUND: Previous reports suggested that rituximab may impair stem cell collection and posttransplant engraftment in lymphoma patients undergoing autologous hematopoietic progenitor cell transplantation. STUDY DESIGN AND METHODS: A prospective biologic allocation study examined the effect of adding rituximab to a mobilization regimen of plerixafor and granulocyte-colony-stimulating factor (G-CSF) for patients with CD20+ lymphoma compared with CD20- lymphoma patients mobilized without rituximab. The primary endpoint was safety of the rituximab-containing regimen; secondary endpoints compared the efficiency of stem cell collection, posttransplant engraftment, graft characteristics, mobilization kinetics, immune reconstitution, and engraftment durability between the cohorts of patients with CD20+ and CD20- lymphoma. RESULTS: Fifteen subjects assigned to each treatment arm were accrued. Both mobilization regimens had similar toxicities. The median number of CD34+ cells collected (7.4 × 10(6) /kg vs. 6.4 × 10(6) /kg) and the median numbers of days of apheresis needed to collect stem cells were not different between the CD20+ and CD20- cohorts. No significant differences in neutrophil engraftment (median, 13.5 days vs. 13 days) or platelet engraftment (22 vs. 21 days) or in graft durability were seen comparing patients with CD20+ versus CD20- lymphoma. There were no significant differences in the kinetics of blood T-cell or natural killer-cell reconstitution comparing the two groups. B-cell reconstitution was delayed in the CD20+ lymphoma group, but this did not translate into a significant increase in infectious complications. CONCLUSION: Rituximab can be safely added to the combination of plerixafor and G-CSF as a mobilization strategy without excess toxicity or posttransplant engraftment delays for patients with chemosensitive lymphoma undergoing autologous hematopoietic progenitor cell transplantation.


Subject(s)
Antibodies, Monoclonal, Murine-Derived/adverse effects , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Heterocyclic Compounds/adverse effects , Heterocyclic Compounds/therapeutic use , Lymphoma/drug therapy , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Benzylamines , Cyclams , Granulocyte Colony-Stimulating Factor/metabolism , Heterocyclic Compounds/administration & dosage , Humans , Lymphoma/metabolism , Lymphoma/therapy , Rituximab , Stem Cell Transplantation
2.
Immunol Res ; 29(1-3): 197-208, 2004.
Article in English | MEDLINE | ID: mdl-15181282

ABSTRACT

CD137 (4-1BB), is an inducible T-cell costimulatory receptor and a member of the tumor necrosis factor receptor (TNFR) superfamily. It is expressed on activated T cells and activated natural killer (NK) cells, but is constitutively expressed on a population of splenic dendritic cells (DCs). The natural counter receptor for CD137 is 4-1BB ligand, a member of the TNF superfamily that is weakly expressed on naïve or resting B cells, macrophages, and DCs. Upon activation, the level of 4-1BBL expression increases on these cells. In T cells CD137-induced signals lead to the recruitment of TRAF family members and activation of several kinases, including ASK-1, MKK, MAPK3/ MAPK4, p38, and JNK/SAPK. Kinase activation is then followed by the activation and nuclear translocation of several transcription factors, including ATF-2, Jun, and NF-kappaB. CD137-mediated T-cell costimulation as measured by enhanced proliferation and cytokine production can be induced by anti-CD137 monoclonal antibodies (MAbs) or by employing immobilized 4-1BB ligand. In addition to augmenting suboptimal TCR-induced proliferation, CD137-mediated signaling protects T cells, and in particular, CD8+ T cells from activation-induced cell death (AICD). Although studies with CD137-deficient or 4-1BBL-deficient mice failed to demonstrate any loss of essential immunological function, or other noteworthy deficits, we have found that 4-1BBL-deficient mice failed to generate a strong antiviral immune response following lymphocytic choriomeningitis virus (LCMV) peptide vaccination. We further found that although compromised, the immune response to LCMV vaccination in these mice could be fully restored by injecting them with anti-CD137 MAbs at the time of vaccination. Finally, we have found that injecting normal mice with anti-CD137 MAbs had profound effects on their ability to develop immune responses to allo- and autoantigens. The results of these studies discussed in this article provide a rationale for assessing the potential use of anti-CD137 MAbs for therapeutic purposes.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Neoplasms/drug therapy , Receptors, Nerve Growth Factor/antagonists & inhibitors , Receptors, Tumor Necrosis Factor/antagonists & inhibitors , Animals , Antibodies, Monoclonal/immunology , Antigens, CD , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Clonal Anergy/immunology , Disease Models, Animal , Humans , Lupus Erythematosus, Systemic/immunology , Lymphocyte Activation , Lymphocytic choriomeningitis virus/immunology , Mice , Mice, Inbred Strains , Neoplasm Transplantation/immunology , Neoplasms/immunology , Receptors, Nerve Growth Factor/immunology , Receptors, Tumor Necrosis Factor/immunology , Tumor Necrosis Factor Receptor Superfamily, Member 9
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