Fractionated doses of gemtuzumab ozogamicin with escalated doses of daunorubicin and cytarabine as first acute myeloid leukemia salvage in patients aged 50-70-year old: a phase 1/2 study of the acute leukemia French association

This Phase 1/2 study aimed to determine optimal doses of daunorubicin (DNR; mg/m²) and cytarabine (mg/m²) to be combined with fractionated doses of gemtuzumab ozogamicin (GO, Mylotarg®; 3 mg/m² on day 1, 4, and 7) satisfying safety requirements. Three dose levels of DNR/AraC were investigated namely (45, 100), (60, 100), and (60, 200). Patients included were acute myeloid leukemia in first relapse, aged 50–70 years. Hematological recovery was 31 days for neutrophil and 32 days for platelet counts. A documented infectious episode > Grade 2 occurred in 11/20 patients (55%). None of the 20 patients had signs of veno‐occlusive disease. Overall, eleven patients reached complete remission (CR), two CR with incomplete platelets recovery. The results showed that combination of fractionated GO doses with DNR at 60 mg/m²/d for 3 days and cytarabine at 200 mg/m²/d for 7 days is tolerable and could be further investigated in the front‐line therapy. Am. J. Hematol., 2012. © 2011 Wiley Periodicals, Inc.     

Anti-CD20 IgA can protect mice against lymphoma development: evaluation of the direct impact of IgA and cytotoxic effector recruitment on CD20 target cells

Background

While most antibody-based therapies use IgG because of their well-known biological properties, some functional limitations of these antibodies call for the development of derivatives with other therapeutic functions. Although less abundant than IgG in serum, IgA is the most abundantly produced Ig class in humans. Besides the specific targeting of its dimeric form to mucosal areas, IgA was shown to recruit polymorphonuclear neutrophils against certain targets more efficiently than does IgG1.

Design and Methods

In this study, we investigated the various pathways by which anti-tumor effects can be mediated by anti-CD20 IgA against lymphoma cells.

Results

We found that polymeric human IgA was significantly more effective than human IgG1 in mediating direct killing or growth inhibition of target cells in the absence of complement. We also demonstrated that this direct killing was able to indirectly induce the classical pathway of the complement cascade although to a lesser extent than direct recruitment of complement by IgG. Recruitment of the alternative complement pathway by specific IgA was also observed. In addition to activating complement for lysis of lymphoma cell lines or primary cells from patients with lymphoma, we showed that monomeric anti-CD20 IgA can effectively protect mice against tumor development in a passive immunization strategy and we demonstrated that this protective effect may be enhanced in mice expressing the human FcαRI receptor on their neutrophils.

Conclusions

We show that anti-CD20 IgA antibodies have original therapeutic properties against lymphoma cells, with strong direct effects, ability to recruit neutrophils for cell cytotoxicity and even recruitment of complement, although largely through an indirect way.Key words: Anti-CD20 IgA, lymphoma, FcαRI     

Chronic meningococcemia cutaneous lesions involve meningococcal perivascular invasion through the remodeling of endothelial barriers

Chronic meningococcemia is a form of sepsis with frequent polymorphous skin lesions. Both in vivo and in vitro data suggest that, in these lesions, meningococci gain access from the capillary lumen to the peripheral extravascular compartment, in the absence of vascular dislocation, through a paraendothelial route.     

Effect of spinal immobilisation devices on radiation exposure in conventional radiography and computed tomography

Trauma patients at risk for, or suspected of, spinal injury are frequently transported to hospital using full spinal immobilisation. At the emergency department, immobilisation is often maintained until radiological work-up is completed. In this study, we examined how these devices influence radiation exposure and noise, as a proxy for objective image quality. Conventional radiographs (CR) and computer tomography (CT) scans were made using a phantom immobilised on two types of spineboard and a vacuum mattress and using two types of headblocks. Images were compared for radiation transmission and quantitative image noise. In CR, up to 23 % and, in CT, up to 11 % of radiation were blocked by the devices. Without compensation for the decreased transmission, noise increased by up to 16 % in CT, depending on the device used. Removing the headblocks led to a statistically significant improvement in transmission with automatic exposure control (AEC) enabled. Physicians should make an informed decision whether the increased radiation exposure outweighs the risk of missing a clinically significant injury by not making a CR or CT scan. Manufacturers of immobilisation devices should take radiological properties of their devices into account in the development and production process.