QJM Advance Access originally published online on October 8, 2008
QJM 2008 101(12):991-992; doi:10.1093/qjmed/hcn133
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Response
Sir,We fully acknowledge the interesting study by Dr Ronald Taylor and colleagues from the University of Virginia School of Medicine, in Charlottesville.1
Incidentally, we were not aware of this study when we decided to treat our first patient with advanced CLL resistant to multiple treatment modalities including fludarabine and rituximab, with a combination of rituximab and fresh frozen plasma (FFP), as a source of complement.2
We hypothesized that since deficiencies in the complement system have been reported in advanced CLL3 and complement-dependent cytotoxicity (CDC) is an important mechanism of rituximab action4—providing complement-rich FFP may potentiate the action of rituximab.
Our point of departure was independent and similar to that of Dr Taylor and his group, namely, the lower efficacy of rituximab in CLL as compared to lymphomas.1,2
We fully appreciate the elegant and convincing studies done by the group from Virginia who demonstrate complement consumption in vitro and in vivo with binding of rituximab to CD20+ CLL cells as well as associated reduced cytotoxicity of rituximab restored by the addition of complement or normal human serum.1 However, their CLL patients were not selected for advanced disease or refractoriness to multiple treatment modalities including rituximab, and their paragraph entitled ‘Therapeutic implications,’1 although devoted to possible ways to apply their findings in therapeutic practice, does not mention adding complement, such as by using a combination of FFP and rituximab. Nevertheless, Dr Ronald Taylor and colleagues have contributed to the understanding of the dramatic effect of rituximab/FFP in treatment-refractory advanced CLL first observed by our group in the first series of CLL patients treated with this combination.
The Hebrew University-Hadassah School of
Medicine, Jerusalem and Sackler Faculty of
Medicine, Tel Aviv, Israel
References
1. Kennedy AD, Beum PV, Solga MD, DiLillo DJ, Lindorfer MA, Hess CE, et al. Rituximab infusion promotes rapid complement depletion and acute CD20 loss in chronic lymphocytic leukemia. J Immunol (2004) 172:3280–8.
2. Klepfish A, Schattner A, Ghoti H, Rachmilewitz EA. Addition of fresh frozen plasma as a source of complement to rituximab in advanced chronic lymphocytic leukaemia. Lancet Oncol (2007) 8:361–2.[CrossRef][Web of Science][Medline]
3. Schlesinger M, Broman I, Lugassy G. The complement system is defective in chronic lymphocytic leukaemia patients and in their healthy relatives. Leukaemia (1996) 10:1509–13.[Web of Science][Medline]
4. Di Gaetano N, Cittera E, Nota R, Vecchi A, Grieco V, Scanziani E, et al. Complement activation determines the therapeutic activity of rituximab in vivo. J Immunol (2003) 171:1581–7.
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