ABSTRACT
Obinutuzumab is a novel glycoengineered, type-II anti-CD20 monoclonal antibody that was recently developed to treat follicular lymphoma (FL), the most prevalent subtype of indolent B-cell lymphoma. Several intensely hypermetabolic lesions (SUVmax: 40) were identified in the post-mediastinal and paraaortic lymph nodes by 18F-FDG-PET maximum-intensity projection images of a 58-year-old man who presented with systemic lymphadenopathy. A biopsy at the time of laparotomy definitively diagnosed grade 1 FL. The patient was given the recommended standard premedication, comprising acetaminophen (1000 mg), diphenhydramine (50 mg), and dexamethasone (20 mg), and then started on six cycles of obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). However, the patient developed severe hypotension and dyspnea about 15 min after starting obinutuzumab. It was difficult to differentiate between a possible allergic reaction and infusion-related reaction. A pleural effusion was drained to reduce the tumor burden, after which a single course of CHOP was started. Rituximab (R) was added 10 days later without incident, and the patient completed six cycles of the R-CHOP therapy without adverse events. We conclude that R-CHOP was safe for administration to patients who react to infused obinutuzumab. Such patients should be carefully monitored during R infusion, given the risk of cross-reactivity.
Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Lymphoma, Follicular/drug therapy , Rituximab/administration & dosage , Administration, Oral , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Humans , Infusions, Intravenous/adverse effects , Lymphoma, Follicular/diagnostic imaging , Male , Middle Aged , Positron-Emission Tomography , Prednisone/administration & dosage , Self Administration , Treatment Outcome , Vincristine/administration & dosageABSTRACT
INTRODUCTION: It is expected that expression levels in the peripheral blood mononuclear cells (PBMC) of IFNAR2, a subunit of the interferon (IFN) receptor, may be a marker for predicting IFN response. In the present study, we have established a rapid and convenient method for assaying IFNAR2, using flow cytometry. METHODS: Fifty microliters of whole blood from healthy volunteers was treated with an anti-IFNAR2 antibody and stained with a Fluorescein isothiocyanate (FITC)-conjugated secondary antibody. In addition, the cells were stained with subset-specific antibodies conjugated with phycoerythrin (PE) and PE covalently linked to cyanin 5 at the same time. The mean FITC-fluorescence intensities were analyzed separately by gating on subset-specific regions. RESULTS: IFNAR2 was detected in most lymphocytes, monocytes, and granulocytes, although IFNAR2 expression was higher in the monocytes and granulocytes than in the lymphocytes. The intra- and interdaily variations of IFNAR2 in lymphocytes, monocytes, and granulocytes were small. Among the lymphocyte subsets, IFNAR2 showed high expression in natural killer (NK) cells and low expression in T lymphocytes. The effect of IFN-alpha on IFNAR2 expression was examined in vitro. A down-regulation of IFNAR2 was observed by IFN-alpha above 100 IU/ml. DISCUSSION: This assay may be useful for examining IFNAR2 in various leukocyte subsets, separately, as well as providing a rapid and easy method for monitoring expression of type I IFN receptors.
Subject(s)
Flow Cytometry/methods , Leukocytes/metabolism , Receptors, Interferon/metabolism , Fluorescein-5-isothiocyanate , Humans , Interferon-alpha/pharmacology , Ion Channel Gating , Lymphocyte Subsets , Membrane Proteins , Phycoerythrin , Receptor, Interferon alpha-betaABSTRACT
Although interferon (IFN)-alpha and IFN-gamma have been reported to exhibit a synergistic antiviral effect through the different signaling pathways in vitro, their therapeutic efficacy is not well defined in vivo. The current study was carried out to investigate the combined antiviral effect in a model of mouse hepatitis virus Type 2 (MHV-2) infection, in which fulminant hepatitis is developed. MHV-2 was injected intraperitoneally into 4-week-old ICR mice, IFN or the vehicle was administered intramuscularly for 5 days, and the antiviral effect was evaluated based on survival periods, liver histology, serum alanine transaminase (ALT) levels, and MHV-2 virus titers in the liver tissues. The animals in the group treated with a combination of IFN-alpha and IFN-gamma survived for longer periods than the groups treated with IFN-alpha alone and IFN-gamma alone (IFN-alpha 10(3) (IU/mouse)/-gamma 10(3) vs. IFN-alpha 10(3), P < 0.005; IFN-alpha 10(3)/-gamma 10(3) vs. IFN-gamma 10(3), P < 0.001). This is consistent with the lower levels of hepatocellular necrosis and serum ALT and the decreased titers of MHV-2 virus in the liver tissues (48 hr, P < 0.001; 72 hr, P < 0.001). These findings indicate that a combination of IFN-alpha and IFN-gamma exhibits a synergistic antiviral effect on MHV-2 infection. The biology of MHV-2 is quite different from that of human hepatitis viruses; however, these results suggest the beneficial combined therapy of IFN-alpha and IFN-gamma for the treatment of human viral hepatitis.
