In all the excitement about the research being presented at ASH and ASCO and EHA on the new therapies for CLL, it is important to remember that infection, mostly respiratory, is still the final grim chapter for most of us. 50-80% of all deaths in CLL are from infections with pneumonia accounting for 40%. Streptococcus Pneumoniae (the bacteria formerly known as pneumococcus) is the leading bad actor. CLL is after all a cancer of the immune system. Dr. Wierda and others are working on ways to reboot our immunity as detailed in this prior post
from ASCO 2013, but that is the future, not our present reality.
IVIG can help by relying on the kindness of thousands of strangers loaning their antibodies to offer us passive immunity. It is potent partial fix, but it is expensive and temporary, and like any infusion, especially a pooled blood product, it carries risks.
Vaccines offer the promise of the more potent active immunity, where we form our own more durable antibodies. The problem has been that they usually don't work. We are wimps at working antibodies. Our clonal B cells mess up our ability to form antibodies. whopping 85% of us have low levels of immunoglobulins and our cellular immunity is not so great either.
But there may be some good news from an abstract presented at the annual meeting of the EHA (European Hematology Association).
Many of patients are all too well aware of our dismal response rates to most killed vaccines. Live vaccine such as the one for shingles or herpes zoster are contra-indicated. Because of our impaired immunity, we just don't form adequate antibodies when given a flu or other shot. And worse, we run the risk after being jabbed with a live attenuated or weakened viral vaccine version of the very agent that we are supposed to be protected against running amuck in our immuno-compromised bodies.
The late CLL champion and researcher, Dr. Terry Hamblin, suggested dual dosing of killed vaccines with ramping up our antibody formation by taking weeks of a histamine 2 blocker between shots. Not much data to back up the idea. He did review a 2007 paper on an earlier conjugated killed vaccine Prevnar 7. His post
offers a nice complement to this for those wanting more background on the pneumonia vaccines.
We all miss the wisdom of Dr. Hamblin.
The CDC has a protocol
about the optimum order and spacing of the vaccines, but that is really just making the best of a bad situation. Bottom line: best to get the new conjugated vaccine first.
This abstract from EHA 2014 is important because it provides some hope and some data for us who are so immune compromised.
A little background. There
are two major commercially available vaccines to prevent pneumonia is the USA.
Pneumovax 23 is based on asking our humeral immune system to
recognize and be ready to attack based on
presenting a polysaccharide (essentially a long
sugar) that will trigger our plasma cells (B cell are the precursors
to these cellular antibody factories) to fight against the 23 most
common flavors of pneumococcus. Prevnar 13, the newer vaccine for adults, is
conjugated to a protein and is more alerting to our immune systems,
though it cover ten less serotypes.
The data is encouraging.
While 100% of the control (normal immunity) population formed antibodies predictive of protecting
against future infections, a still impressive 58% of CLL patients did the same.
Compare that to the old vaccine results of from near zero to 25% response rates.
As one might expect based
on all the prior research, those of us who do the best are those who are early
in our disease with the higher levels of antibodies.
It is more complicated. As the
name implies, Prevnar 13 only protects against 13 of the roughly 90 subtypes of
Strep. Pneunomiae and obviously none of the infections caused by other
pathogens. Moreover, as the vaccine is more widely used in different
populations, the prevalence of the various subtypes causing us misery switches
away from those covered by the vaccine. Those clever bacteria.
Another concern is that there is
certainly no guarantee that just because our antibodies doubled that we will
still have the immune resources to fight off a dangerous infections. We need
more than antibodies. We need organized and functional T cells, something we
are often sorely missing.
This study did not show that we got less infections. That would be a much longer and more robust trial. This trial just showed that we formed more protective antibodies with the new vaccine.
And that is a helpful
So here is the take away.
We should get vaccinated
as soon as we are diagnosed. Prevnar 13 is the better choice for the first jab, or even the second.
I have pasted the actual abstract from the EHA
below, as I found their web site cumbersome to navigate.
6. Chronic lymphocytic leukemia and
related disorders - Clinical
EVALUATION OF IMMUNE RESPONSE TO
13-VALENT PNEUMOCOCCAL CONJUGATED VACCINE (PCV13) IN PATIENTS WITH CHRONIC
2, Ewelina Grywalska3,
of Clinical Oncology, Holycross Cancer Center, 2Faculty
of Health Science, The Jan Kochanowski University, Kielce, 3Department
of Clinical Immunology, 4Department
of Clinical Transplantology, Medical University of Lublin, Lublin, Poland
Background: Chronic lymphocytic leukemia (CLL) is a lymphoproliferative
disorder associated with severe impairment of the immune system in a
substantial proportion of patients. This is directly linked with an increase in
susceptibility to bacterial and viral infections. About 50 to 80% of patients
diagnosed with CLL die from infectious complications. Most infections in CLL
patients is caused by capsular bacteria: Streptococcus pneumoniae and
Haemophilus influenzae. Patients with CLL who have low levels of
antipneumococcal antibody are particularly at risk for severe and recurrent
pneumococcal infections. In the U.S. and in many EU countries, vaccinations
against Streptococcus pneumoniae are recommended for immunocompromised
patients, such as patients with CLL. For many years, 23-valent pneumococcal
polysaccharide vaccine (PPV23) was used. Antibody responses to PPV23 vaccine
are inadequate in most patients with CLL, that induced response only in about
20-25 % of patients. Since 2012, in the prevention of pneumoccocal infections
in immunocompromised adults, 13-valent pneumococcal conjugate vaccine (PCV13)
has been used that efficacy in patients with CLL has not yet been studied
aim of this study was to assess the efficacy of vaccination in patients with
CLL using PCV13.
Methods: The study included 24 previously untreated patients with CLL
in stage 0 - 2 according to Rai calssification and 15 healthy subjects as a
control group. The percentage of plasma cells, defined as CD19+/++IgD/CD27, was
analysed before vaccination and 7 days after the immunization, the level of
specific anti-pneumococcal antibodies and the level of IgG and IgG1, IgG2,
IgG3, IgG4 immunoglobulin subclasses were evaluated prior to vaccination and 4
weeks after vaccination.
Results: The positive response to vaccination was defined as at least
a two-fold increase in specific anti-pneumococcal (anticapsular) antibody
titers as compared to the titer prior to the vaccination. Such a criterion of
response was fulfilled in 100% of healthy subjects and in 58.3% of the patients
with CLL. The percentage of plasma cells after vaccination was significantly
lower (p < 0.0001) in patients with CLL comparing to the control
group. Both in patients with CLL as well as healthy subjects, there was a
statistically significant increase in the level of IgG2 subclass after
vaccination (p = 0.0301). The patients with adequate antibody response to PCV13
had significantly less advanced stages of CLL, higher total IgG levels and IgG2
and IgG4 subclass levels. There was no no significant vaccine-related
reactions, no increase in peripheral blood lymphocyte count and no
changes in laboratory markers of disease activity.
Summary/Conclusion: Protective immunization of patients with CLL using the PCV13
is safe and induces an effective immune response in a large proportion of
patients. To achieve the optimal postvaccinal response it is recommended to the
use the PCV13 as early as possible after the diagnosis of CLL with
determination of post-vaccination antibody levels.
Keywords: Chronic lymphocytic
leukemia, Infection, Vaccination
Labels: Chronic lymphocytic leukemia, CLL, EHA 2014, immunity, pneumonia vaccines