The Third Wave

There is little doubt that the number of reported infections and even more importantly the number of reported deaths due to H1N1 have decreased greatly over the past few weeks. The trend is clear and to be expected, and it influenced my decision to use the window of opportunity and risk the long flight from India to the USA at this time.

But influenza pandemics come in waves.  We had the first wave early summer of 2009, the second wave in early Fall.  Both of these waves are out of the ordinary, un-seasonal.  In normal years the flu season gets underway in real earnest sometime after Christmas.  Pediatric deaths due to H1N1 have already outstripped the usual numbers for the whole season and I fear the worst is still ahead, in the cold months of deep winter. 

“How We Treat Influenza in Patients With Hematological Malignancies”

The latest edition of “Blood” yet to hit the bookstands has a very important paper that should be mandatory reading for all hematologists taking care of immune compromised patients.  The abstract is below, for your convenience. If you wish to read the full text article, send me a personal email and I will try to point you in the right direction.

Blood.. [Epub ahead of print]

How we treat influenza in patients with hematologic malignancies.

Casper C, Englund J, Boeckh M.

Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States;

The 2009 H1N1 influenza pandemic has heightened the interest of clinicians for options in the prevention and management of influenza virus infection in immunocompromised patients. Even before the emergence of the novel 2009 H1N1 strain, influenza disease was a serious complication in patients with hematologic malignancies receiving chemotherapy or undergoing hematopoietic cell transplantation. Here we review the clinical manifestations of seasonal and 2009 H1N1 influenza and discuss current diagnosis, antiviral treatment, and prophylaxis options. We also summarize infection control and vaccination strategies for patients, family members, and caregivers.
PMID: 20009037

We kind of knew our guys were at more risk.  This article gives us chapter and verse, expert guidance on what to expect, what to do and how best to protect not jus the patients with blood cancer but also their families and care givers. I have tried to summarize the major points below:

Early Stage:

  • Patients with blood cancers are more likely to get infected. Like we did not know that already.
  • Initial upper respiratory infection in blood cancer patients may lack the usual symptoms – fever, fatigue, body ache. The theory is that in immune-compromised  patients immune responses are just too weak. These symptoms are signs that a fight is going on. Our guys do not put up much of a fight, especially if they are on corticosteroid therapy. The most you may notice is a case of sore throat, sniffles, mild headache – easily dismissed as trivial.
  • They may not look or feel sick, but they are shedding virus particles liberally, increasing risk to their caregivers. This article and others point out that immunocompromised patients shed virus copiously for longer periods of time, compared to healthy people.

Disease Progression Deeper into the Lungs

  • The most serious consequence of influenza infection is pneumonia, leading to lung injury and death.  I must have emphasized this point a dozen times by now: the single biggest cause of death in CLL patients is pneumonia.
  • This paper reports that progression from upper to lower respiratory tract happens in about a week in patients with blood cancers. That is a short fuse!
  • This viral pneumonia is frequently complicated by additional bacterial and fungal infections.
  • The single biggest risk factor is lymphopenia – decreased white blood count.  This may sound confusing.  Most of our guys have sky high WBC! True, but the high WBC is almost entirely made up of useless cancerous CLL cells. T-cell counts are not separately measured, but if you have been through fludarabine, pentostatin or Campath therapy, very likely you have low T-cell counts. If on top of that you also have neutropenia (low neutrophil counts), you are at risk.  The high WBC  and ALC in a CLL patient just means the  tumor load is high, but it does NOT mean you have healthy fighting troops.
  • Use of high dose corticosteroids increases the length of time that the patient is shedding live virus.
  • Influenza infection is one of the most serious causes of death in recently transplanted patients.
  • The authors suggest that more vigilance is required in monitoring immune compromised patients precisely because they may not show many of the common symptoms of fever, fatigue and body-ache. It pays to be more suspicious than otherwise.
  • If you are a CLL patient and you have influenza, the authors suggest you should get a chest scan to rule out lower tract infection and pneumonia.
  • Not everyone is in the same boat:

“A wide spectrum of immunosuppression exists among patients with hematologic malignancies, ranging from chemotherapy to allogeneic transplantation following myeloablative conditioning with vivo or ex vivo T cell depletion or refractory graft versus host disease.  Underlying conditions that complicate influenza disease in otherwise immunocompetent persons may be present, including diabetes, obesity, and pulmonary or cardiac disease.”

The “Hutch” Experience

The Seattle Hutchinson Cancer Center is one of our preeminent expert centers.  They have probably done more stem cell transplants than just about any other center in the world.  As you can imagine, they would be particularly concerned about protecting their patients, since transplant patients soon after the procedure are among the most immune compromised folks you can find.

Hutch instituted a policy of aggressive monitoring, assuming the worst sooner rather than later, aggressive anti-viral therapy (including high dose and intravenous administration of multiple antivirals and antibiotics) as well as IVIG therapy as appropriate.  You will have to read the full text of the paper to get all the details.

So, did all the extra work and sometimes over the top vigilance make a difference?  I am very relieved to report it did, otherwise I would be just bringing you bad news without giving you any hope for prevention.  Below is the chart of H1N1 detection in the community at large (Puget Sound, Seattle area) compared to the patients treated at the Hutch.

As you can see, the green line representing the incidence of H1N1 in the Seattle WA community was about the same as the rest of the country.  There was the first wave peaking in early summer, followed by the more recent second wave peaking towards the end of May, 2009, dribbling down to present low levels.

Comparing the green community incidence to the blue (seasonal flu) and red (H1N1 flu) incidence rates at the Hutch is truly impressive.  Hutch was able to stop this infection in its tracks!  The blue and red lines are just about hugging the zero count!  Way to go guys.  I take my hat off to the hard work and perseverance of the Hutch staff in protecting their patients. This is remarkable success.

What contributed to the effectiveness of the Hutch program?  What are some of the take home messages for us?  Below is a chart of the various components of the Hutch program.  Some of the things they found very effective are quite simple, things that you can do yourself at home.

Take home points

  • It is not yet time to call this sucker a thing of the past. If I am not mistaken, there will be a third wave soon, it is gathering speed as I write.
  • Our guys are more at risk of getting infected and dying from it.
  • Simple things like hand washing, social distancing, getting the vaccination when it is available – all of these will help.
  • CLL patients are not typical in how they show symptoms. They may not have the usual high fever, fatigue, body ache.  You are smart not to ignore more “trivial” symptoms such as sniffles, sore throat and mild headache.
  • Take the Hutch paper and the link below from the CDC to your oncologist and GP if they are still complacent about your high risk profile.
  • http://www.cdc.gov/h1n1flu/immunosuppression/index.htm
  • No one can be a better advocate for you than you yourself. Take care, stay healthy this up-coming flu season!