Sunday, November 23, 2008

"If I ruled the world" Leslie Bricusse and Cyril Arnadel

You say you want a revolution.

The Beatles

This is a followup to my post of November 11, about the herpes zoster vaccine and would be of interest to those with CLL and those who are frustrated with trying to get the government to change.

It started as I was reviewing a paper on herpes zoster for publication for medical education.  I came across this frightening reference from the CDC, specifically the Advisory Committee on Immunization Practices (ACIP).

"Patients with leukemia, lymphoma, or other malignancies whose disease is in remission and whose chemotherapy has been terminated for at least 3 months can receive live-virus vaccines.”

We all know patients with CLL should NEVER  receive a live vaccine and herpes zoster vaccine is a live attenuated virus.

Here's the letter I wrote:

Subject: Concerns about the safety of the herpes zoster vaccine in patients with chronic lymphocytic leukemia

Dear Dr....,

As a both a practicing physician and as a patient with a history of CLL (Chronic Lymphocytic Leukemia)  I am writing you in your capacity as a member of the Advisory Committee on Immunization Practices.  I am writing to both urgently express my concerns and to respectfully ask for your help with the published recommendations of the ACIP as they relate to the safety of the herpes zoster vaccine for patents with CLL in remission.

In what appears to be clarification of the package insert, the section on Immunocompromised Persons under the heading Contradictions in the current Prevention of herpes zoster. Recommendations of the Advisory Committee on Immunization Practices (ACIP) contains the following:

           • Persons with leukemia, lymphomas, or other malignant neoplasms affecting the bone marrow or lymphatic system. However, patients whose leukemia is in remission and who have not received chemotherapy (e.g., alkylating drugs or antimetabolites) or radiation for at least 3 months can receive zoster vaccine.

The second sentence is contrary to the standard of practice I have encountered in the hematology-oncology community and what I have found in the CLL literature. Those who treat CLL patients recognize that even in a complete remission with no minimal residual disease, their patients remain immunodeficient. They generally advise these patients to avoid live vaccines at any time in the course of their disease.

Certainly a three-month remission would not qualify such patients as sufficiently immunocompetent to receive a live vaccine.

The following is an example:

"[P]atients with CLL should be regarded as immunodeficient as far as vaccination with live attenuated organisms is concerned and these should be avoided."

Hamblin, D. and Hamblin, T. J. The immunodeficiency of chronic lymphocytic leukaemia British Medical Bulletin 2008; 87: 49–62 A.

The following advice was given to patients by two recognized world authorities on CLL:

" [P]atients with CLL should never have live vaccines." Dr T. J.Hamblin, Professor of Immunohaematology Southampton 1986 to present. Honorary Consultant Haematologist Kings College Hospital, London, 2004- present.

"CLL patients should not get the shingles vaccine as it is a live virus." Dr. Richard Furman, assistant professor, Division of Hematology and Oncology, Weill Medical College at Cornell University, New York, NY.

The decision to offer the herpes zoster vaccine is often made by a primary care provider who would not question the guidelines of ACIP.

For the safety of those with patients with CLL in whom any live vaccination poses a risk, I respectfully ask you that you urgently revisit the latest guideline. Please consider enlisting the aid of treating hematologists-oncologists specializing in CLL in drafting the revision.

I am happy to offer my help in any way I can to facilitate the process.

Thank you

Sincerely

Brian Koffman MDCM FCFP, DAAFP, MS Ed

Here's the considered and thoughtful, but unbudging response:

Subject: FW: Concerns about the safety of the herpes zoster vaccine in patients with chronic lymphocytic leukemia

Dear Dr. Koffman,

Thank you very much for your sharing your concerns regarding recommendations by the Advisory Committee for Immunization Practices (ACIP) that the vaccine for herpes zoster (HZV) be offered to persons 60 and older with CLL in remission. This is a very reasonable question, and I am eager to respond.

In way of background, the ACIP made its decision with input from experts who considered issues of safety as well as efficacy, feasibility and of cost-effectiveness. Needless to say, input was obtained from physicians with expertise in managing patients with cancer and other causes of immunocompromise. The ACIP strives to be very deliberate, and does not apply a one-size-fits-all approach regarding vaccine recommendations or patients.

Many vaccine preventable diseases (e.g., measles, varicella) are severe and even life threatening in immunocompromised persons, and decisions regarding vaccination with live vaccines therefore involve careful consideration of risks and benefits. In certain instances, live vaccines are recommended for defined categories of immunocompromised persons at high risk of these diseases. This same calculation is appropriate for HZV since HZ, too, poses an extremely high burden of disease among immunocompromised persons. In fact, depending on the specific condition, the incidence of HZ is increased orders of magnitude as compared to unaffected age-matched persons, and the spectrum of illness from HZ is much more severe as well, resulting at times in dissemination, encephalitis, severe ocular involvement, or death.

A number of key considerations distinguish HZV from other live vaccines

* Virtually all adults aged 60 and over are at risk of HZ (i.e., are infected with latent varicella zoster virus, or VZV). In contrast to other live vaccines, HZV does not protect by preventing infection but by preventing reactivation of this latent infection, which is much more likely in immunocompromised persons. A strategy of vaccinating household contacts would not protect a person with CLL (in contrast, say, to vaccinating household contacts with varicella vaccine to protect a child with leukemia).

* People receiving HZV have preexisting immunity to VZV. While second episodes of chickenpox occasionally occur, second VZV infections remain uncommon even among the most profoundly immunocompromised persons, and those rare episodes that do occur are not severe. Immunity to VZV in such patients appears to be adequate to protect against disseminated infection from the wild-type, natural VZV virus, and the risk of adverse effects from live-attenuated VZV contained in HZV should be correspondingly lower.

* In fact, there is empiric evidence to support the safety of HZV in immunocompromised persons. In early trials, the live-attenuated VZV used in varicella vaccine as well as HZV was administered to hundreds of profoundly immunocompromised children with leukemia in remission and *without* preexisting immunity to VZV, and the vaccine was well tolerated. These children tolerated subsequent second doses of the vaccine even better. Live attenuated VZV has since been safely and effectively used in many more children with other immunocompromising conditions such as transplant recipients and HIV infection. Live attenuated VZV is now recommended in HIV-infected persons without prior immunity to VZV. Finally, live attenuated VZV has also been used in HIV-infected children with prior varicella infection and immunity. As would be expected, the children tolerated the vaccination very well.

* General guidance on use of live attenuated vaccines by persons with leukemia has been evaluated by ACIP and published in their General Recommendations on Immunization (
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5515a1.htm ) published Dec. 2006. The document states that "Patients with leukemia, lymphoma, or other malignancies whose disease is in remission and whose chemotherapy has been terminated for at least 3 months can receive live-virus vaccines."

Given the potential severe, life threatening HZ in persons with CLL in remission, and the considerations regarding the safety of this vaccine, the ACIP recommends that the vaccine should be used in such circumstances.

Thanks again for contacting us. I wish you a complete and speedy cure of your illness. Please feel free to share this correspondence with your treating physician, and do feel free to contact me if you wish to discuss this further (I can be reached at the number below).

Best wishes,

Dr...

I was unhappy with the result and forward this correspondence and others between myself and various doctors at the CDC to the well respected world CLL expert, Dr . Terry Hamblin.

Please check out his detailed, lucid and balanced approach on his wonderful post in his blog. http://mutated-unmuated.blogspot.com  If you have CLL, his blog is required reading. You can tell I am a big fan of Dr Hamblin and what he does for the CLL community. 

After you have read Dr Hamblin's post, please consider discussing this with your own oncologist and maybe ask them to write the CDC's ACIP if they are as concerned as I remain.

Maybe if dozens of oncologists write, they may reconsider. They have been polite, prompt, responsive and detailed, but they remain unconvinced. 

I think we need to be equally as polite and detailed, but we also need persistence and greater numbers.

I have not included names but if you go to the links you can find to whom your oncologist should write.  If you do decide to follow through on this, I want you to have done your homework and due diligence. You might even want to draft a short note to help get your doctor started. It could be very simple. Have the links to the ACIP printed out. Have the addresses. Most docs are too busy, but if you make it easy for them, they are more likely to help.

I have no doubt the doctors at the ACIP are concerned, but their background is infectious disease and public health, not heme-onc. 

Let's help them help us.

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1 Comments:

OpenID chemobrain said...

I'm going to write my first blog post for over six months on this subject.

I find it shocking that this is happening.

Andy

November 28, 2008 at 2:41 AM  

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