Mea culpa: The Gritty and Confusing Details of the ACIP Recommendations for the Shingles Vaccine

Seems I missed some of the critical details of the "change."

Not nearly the picture I had portrayed in my last post, so I must share my mistake and thank Dan for elucidating my error.

For those, happily not worried about the minutiae of T cells and B cells and vaccine responses, you might read the following as a lesson I learned in the dangers of wishful thinking and not checking deeply into the facts.

As both a reporter of fact and as a scientist, I must quickly and fully admit and publish my errata.

Others might find a cautionary tale of the arrogance of big government, the dangers of decisions made by bureaucratic committees with their deft ability to impose their will and yet accept no responsibility for the consequences

Here are the details as explained by my friend, Dan who tells the story much better than I could.

Frankly, I am not enthused about the next step.

Brian

I suspect that you’re playing catch-up from your Middle East sojourn (a little rest, and the world is full of work). In that haste, you may have done a quick misread of the CDC-ACIP changes in re the shingles vaccine.

It is my understanding, of which I’m awaiting CDC – ACIP written confirmation, that the CDC – ACIP actually “cleaned-up” their integration between documents. Id est, the broader “General Recommendations on Immunization - Recommendations of the Advisory Committee on Immunization Practices (ACIP) as dated December 1, 2006 / 55(RR15);1-48” with the specific “Shingles Vaccine Information Statement” of 09/11/06 as revised 10/06/09, to better dovetail the latter with the broader 2006 white paper.

The broader “General Recommendations on Immunization …..” of Dec. 2006 has not been modified. The sectional title therein “Vaccination with Live-Attenuated Vaccines” still retains the language “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.” And therefore remains as dated December 1, 2006.

It is my understanding, as of my phone conversation with them today, that the CDC – ACIP has not been provided properly substantiated, valid, reliable, quantitative data for them to change their position. I had a “feeling” of suspecting something like this and is the reason I included in my email to Ron G. the Errata: Vol. 55, No. RR-15 to the still otherwise unmodified General Recommendations on Immunization, et cetera. I’m of the belief that the cornucopia nodes of such lacking data may repose in wait at places like MDACC, The Mayo Clinic, LIJ, NYP-WCMC, Dr. Hamblin’s olde haunts in the UK, in Cologne & Essen in Germany, Barcelona in Spain, Turin and Rome in Italy, et al.

On the other side of the argument, I sense the CDC – ACIP may have derived their position based on manifestations of leukemia other than that of CLL, e.g. childhood leukemia. I intend to follow-up on this aspect, should I receive back an email response. Should this prove to be the case, the extension of their argument as applicable to CLL may be fallacious. I sense the resolution lies with the T cells CD4 cut-off threshold limit, which if I understand correctly ties into Dr. Hamblin's 10/29/09 ACOR CLL posting (see below).

I have provided herewith a recap of past email correspondences and postings, as well as my email today to Dr. Kroger of the CDC – ACIP.

Regards,

Dan C.

Westchester, NY

In brief, let’s recap:

2008, Nov. 22: Dr. Hamblin posts “Shingles vaccine” at his website blog: http://mutated-unmuated.blogspot.com/search?q=shingles+vaccinehttp://mutated-unmuated.blogspot.com/search?q=shingles+vaccine

In paraphrase, the issue is the ACIP stance that the herpes zoster vaccine is safe for CLLers if we have been in remission for only 3 months.

2008, Nov. 24: Your post brings the foregoing issue to the attention of ACOR CLL Listserv members, asking that we bring the ACIP position to our individual doctors (hems/oncs), beseeching each hem/onc that disagrees to write the ACIP accordingly.

2008, Nov. 28: I had emailed you “off-list” to bring your attention to the CDC-ACIP’s “09/11/2006 Shingles Vaccine Information Statement”, noting among other things that it expressly states “- a history of cancer affecting the bone marrow or lymphatic system, such as leukemia or lymphoma”, and that since it’s the more detailed document that it could be argued as controlling. I had also suggested considering confronting them with potential liability issues, i.e., “fear of the law”, in addition to possibly doing one letter signed by numerous CLL mavens. (You did email me back, advising considering & would advise after up coming holidays).

2008, Dec. 17: Dr. Byrd had requested posting within the CLL ACOR Listserv (highlighting & underlining added) “….the varicella zoster virus vaccine which should not be given toCLL patients due to their immunocompromised state. Some practiceners are mistakenly giving this and it places CLL patients at risk. ….” (s/b “practitioners”).

2008, Dec. – 2009, Oct. – since your 11/28/08 posting asked others for action, it’s not surprising the issue waned with time (a phenomena that can be thrown into the baskets of other axioms, like, “I’m from the government and I’m here to help.”). Needless to say, the topic issue similarly comes and goes on the daily CLLSLL Yahoo digests, quite often back and forth on treatments, which Dr. Furman addresses.

2009, Oct. 29: In response to the topic issue again having risen, Dr. Hamblin notes within an ACOR Listserv post (highlighting & underlining added): “……virtually everybody still carries the virus in their nerve cells. The reason that it doesn't reactivate is that we have sufficient specific T cells to control it ….. The ban on shingles vaccine for CLL patients is based on theory not evidence, but it is the safer course. If the vaccine is to be banned then it makes sense to avoid contact with anyone excreting the virus. ….”

2010, Feb. – Mar.: Like the story of Lazarus, the topic of the shingles vaccine for those diagnosed with CLL rises again. On 03/03/10, Ron Goldsmith, ironically in “Phoenix”, AZ, succinctly summarizes the history of the topic, as well as providing the link to Dr. Hamblin’s 11/22/08 clearly written, easily read write-up of the topic’s issue. Noting the “bottom line: Shingles vaccine is not safe for CLL patients.”

2010, Mar. 06: This writer emailed Ron G. a brief of off-lists emails with Brian K. back in late Nov. 2008, providing an updated comparison between “09/11/2006 Shingles Vaccine Information Statement” and 10/06/09 revision. In sum the 2006 version states those with “a history of cancer affecting the bone marrow …” should not get the shingles vaccine, whereas the wording “a history” has been deleted in the Oct. ’09 revision. Moreso, whereas the Oct. 2009 revision additionally has the word “current”, i.e., should not get the shingles vaccine who “has a weakened immune system because of current:”. This writer had also included, i.a., Errata: Vol. 55, No. RR-15 to the still unmodified General Recommendations on Immunization - Recommendations of the Advisory Committee on Immunization Practices (ACIP) as dated December 1, 2006 / 55(RR15);1-48, because this writer found the wording “…can receive varicella and measles vaccine if CD4+ lymphocyte count is >15% …” of interest as possibly worthy for exploring in re CLL. Copied:briankoffman@sbcglobal.net, terjoha, rrfurman@med.cornell.edu.

2010, Mar. 07: Writer received off-list email from Dr. Furman: “It is also very, very important to emphasize that the Shingles vaccine has not been demonstrated to be effective in people with weakened immune systems. Thus, there is no know benefit and the potential for harm, making the risk: benefit ratio not at all favorable.”

2010, Mar. 07: Writer emails Dr. Furman: “….I find it incredulous that the CDC, APIC, et al can make such "no liability recommendations" without valid & reliable supportive documentation in place. There should be in place, readily available, valid and reliable quantifiable and or quantified variables upon which they based their risk evaluation and derived decision(s) to recommend. In absence of this, the first thing that comes to mind is litigation, which is one of the points I suggested to Brian as confronting them with. In reviewing their most recent updates, I walked away with an impression of them being obstinate, pompous, and arrogant. Needless to say, the ACIP has ample exculpatory language, to wit, their usage of such words as "suggestions" and "recommendations"; furthermore, after their rather well organized, rather detailed, flowing spiel, they do effectively shift the end point onto the practitioner, e.g., you, as to deciding what tests, results interpretation & recommendation of decision path to follow. …”

2010, Mar. 10: Brian emails writer: “…think this is a significant improvement in the text that better reflects the current state of knowledge about the safety of the vaccine in patients like me. …”

2010 Mar. 12: To resolve my dissonance, this writer called and spoke with CDC – ACIP Andrew Kroger, M.D. down in GA and subsequently emailed the following:

Start 03/12/10 email to Andrew Kroger:

“Andrew, as per our 2:00 P.M. phone conversation today.

Dan C.

Westchester, NY

In re above, two changes of note:

Æ Sept. ’06 version states “a history of cancer affecting the bone marrow …”, while “a history” has been deleted in Oct. ‘09

Æ Oct. ’09 version now states “has a weakened immune system because of current:”, note the word “current” did not appear in the Sept. ’06 version.

So, l et me just add this note from Dr Furman to bookend this story.

I really think the important piece of information is that there are no efficacy data for the vaccine in CLL patients and I suspect the benefit is likely extremely small given the immunodeficient state of untreated CLL and the even more immunodeficient state after treatment.
With the proven benefit, any risk becomes not worthwhile. I also see acyclovir and its derivatives as being so effective.

Rick Furman

So that's the story, so far. I will keep you posted of the byzantine changes, but I expect no breakthroughs.

Bottom line.

Don't jump to conclusions, happy or sad.

Check all the facts yourself.

Don't expect big anything (government, pharma etc.) to be looking out for you.

Admit your mistakes and correct them asap.

Don't give up spreading the truth.

A Small but Positive Change in recommendations about the Zoster Vaccine

In November of 2008, I helped launch a campaign that eventually involved Drs. Hamblin and Furman and others in changing the recommendations of the Advisory Committee on Immunization Practices (ACIP) about who should not get the live Zoster (shingles) vaccine.

Their recommndations used to read (in part):

• 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.

Now they read (in part):

Who should NOT get the shingles vaccine? NEW MAY 2009

Some people should not get the shingles vaccine:

• People with a weakened immune system as a result of leukemia, lymphoma, or any other blood or bone cancer.
• People being treated with drugs that affect the immune system, including high-dose steroids.

Please notice that there is no longer the three months clean and you are cleared for vaccination. This is a subtle, but important change that better reflects the present state of knowledge about live attenuated vaccine safety for people like me.

The new recommendations happened quietly, so quietly that I missed the change, but I think the CLL community can feel proud about the role we played in nudging the infectious disease and hematology communities out of their silos and closer together in their thinking about how to best serve some of their most vulnerable patients.

Thanks to all those who helped, especially Dr. Hamblin.

This is good news.

"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.

"I've had enough of reading things by neurotic, psychotic,pig headed politicians" John Lennon

"All I want is the truth

Just give some me some truth"

John Lennon

Below is an editied version of the email I sent to Dr. Forman when I mentioned to him my concern about the ACIP recommendation concerning the zoster vaccine, during my office visit yesterday.

If you are a CLL patient, be prepared to be astonished by the advice your government is giving to the medical community.

Dear Dr. Forman,

In the process of reviewing a paper for publication of herpes zoster, I came across this possibly dangerous statement in italics below from "The Prevention of herpes zoster. Recommendations of the Advisory Committee on Immunization Practices (ACIP)" (http://www.guideline.gov/summary/summary.aspx?doc_id=12633&nbr=6541&ss=6&xl=999). You may also read the full recommendations at the web address above.

Immunocompromised Persons

Zoster vaccine should not be administered to persons with primary or acquired immunodeficiency including:

• 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.

As we know, patients with CLL should never have live vaccines. I hope a letter to the authors from a PCP would make an impact. I will do what I can to have the language changed in regards to CLL.  I have started a search for source material on the safety of live vaccines in CLL. I would appreciate your advice and support and any reference material in this effort.

The decision about the offering the HZ vaccine is often made by a primary care provider who would not question the guidelines of ACIP who work under the umbrella of the CDC. Indeed the paper I am reviewing has a case studies that recommends HZ vaccine in a patient with CLL in remission.  If I didn't have personal experience with CLL,  I would not have questioned the recommendation.

Thank you so much,

Sincerely

Your patient and colleague,

Brian Koffman MDCM FCFP, DAAFP, MS Ed

So now it looks like I am not fighting city hall, but the feds. First, I will try to align all my allies in the heme/onc community, and get appropriate references to back up my battle. This guideline must be changed.

If you are not a CLL patient you might be wondering why this has so upset me. A live vaccine might be very very dangerous for anyone with CLL, at any stage of disease. CLL impairs one's immunity, even when in deep remission and a live vaccine can cause havoc when the defences are down.

Let me share this with you.

“On the other hand, patients 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.

Below are quotes from two CLL experts who many of my leukemia friends know too well.

“First, patients 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.

I will keep you posted, though the change will come slowly, it surely will come.

To quote Rabbi Tarfon

It is not your part to finish the task, yet you are not free to desist from it. 

Pirke Avoth 2:16