Yazarlar : Middleton O, Cosimo E, Dobbin E et al.

Yayın : Leukemia

Yayın Yılı : 2014

Pubmed Linki : http://www.docguide.com/complement-deficiencies-limit-cd20-monoclonal-antibody-treatment-efficacy-cll?tsid=5

Konu : Lösemi

Literatür İçeriği :  Monoclonal antibodies (MAbs) form a central part of chronic lymphocytic leukaemia (CLL) treatment. We therefore evaluated whether complement defects in CLL patients reduced the induction of complement-dependent cytoxicity (CDC), using anti-CD20 MAbs rituximab (RTX) and ofatumumab (OFA). OFA elicited higher CDC levels than RTX in all CLL samples examined, particularly the poor prognosis cohorts (11q- and 17p-). Serum sample analyses revealed 38.1% of patients were deficient in one or more complement components, correlating with reduced CDC responses. While a proportion of patients with deficient complement levels initially induced high levels of CDC, on secondary challenge CDC activity in sera was significantly reduced, compared with normal human serum (NHS; P<0.01; n=52). Additionally, high CLL cell number contributed to rapid complement exhaustion. Supplementing CLL serum with NHS or individual complement components, particularly C2, restored CDC on secondary challenge to NHS levels (P<0.0001; n=9). In vivo studies revealed that complement components were exhausted in CLL patient sera post-RTX treatment, correlating with an inability to elicit CDC. Supplementing MAb treatment with fresh frozen plasma may therefore maintain CDC levels in CLL patients with a complement deficiency or high white blood cell count. This study has important implications for CLL patients receiving anti-CD20 MAb therapy.Leukemia accepted article preview online, 02 May 2014; doi:10.1038/leu.2014.146.

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