CAMPATH has been around for about 20 years. It was first discovered by Geof
Hale and Herman Waldmann at Cambridge University, England. It was a rat
monoclonal antibody directed at human lymphocytes. It was an IgM antibody with a
molecular weight of 1 million, much too large a molecule to be used in patients
because it would not diffuse through body tissues. I used it in the 1980s to
purge bone marrow. If you incubate bone marrow with the original Campath it
kills all the lymphocytes in the marrow and therefore that marrow can be used
as an autograft without fear of the lymphoma returning. It was also used in
the pleural cavity to treat pleural effusions caused by lymphoma.

However, in order for it to be used intravenously it had to be altered. The
remarkable story of how the Cambridge scientists did this by genetic
engineering makes interesting reading. Remember it was at Cambridge that monoclonal
antibodies were invented by cesar Milstein who won the Nobel prize, yet didn't
patent them, preferring to donate this remarkable discovery to the world
rather than indulge in anything so venal as making money out of them.

Anyway, eventually the humanized IgG antibody, Campath 1-H became available.
Originally owned by Wellcome it is currently marketed by Berlex in the
States and Schering AG in Europe. It is now manufactured by educating Chinese
hamster ovary cells (CHO cells) to make it in tissue culture. It is directed at
an antigen, CD52, that is on all lymphoid cells, B-cells, T-cells, NK cells
and dendritic cells as well as monocytes and spermatazoa. It has been used in
the rare T-prolymphocytic leukemia (T-PLL) but also in CLL. CD52 is
represented on lymphocytes much more densely than CD20 (the target of rituximab) and
mush smaller quantities (typically 30 mg rather than 350 mg). However, these
smaller doses are more likely than rituxan to cause infusion related side
effects, such as fever, the shakes, pain, low blood pressure etc. Because of this
there has been a tendency to use it subcutaneously rather than intravenously.

Campath is very good at clearing blood and bone marrow and to a lesser
extent spleen of CLL but not so effective against lymph node masses. It also has
the advantage of being more effective against drug resistant CLL, especially
those with p53 mutations.

However this is at the expense of side effects. Because CD52 is present on
all the immune system cells (whereas CD20 is only present on B cells) Campath
is much more immunosuppressive than Rituxan. One of the characteristic
complications is reawakening of CMV infection. This only occurs in people who have
been infected by CMV in the past (usually this is a trivial infection that
the body deals with without bringing it to your attention), but if gets a hold
it is very serious. Therefore patients on Campath are regularly screened for
CMV and if the test is positive they are given gancyclovir to stop it really
coming back. Other serious infections are also a possibility such as EBV
(which can cause Richter's syndrome - an aggressive lymphoma - in CLL),
aspergillus, histoplasmosis, pneumocytis; and also autoimmune conditions like AIHA or
ITP. Therefore, Campath must be used with care, only by physicians who are
familiar with its use, who take the proper precautions.

In the UK Campath is commonly used for stem cell transplants with reduced
intensity conditioning. The combination of fludarabine, busuphan and campath
(FBC) has made it possible to do volunteer matched unrelated transplants on
patients in their 70s without the high mortality rate that was previously seen.