07-31-2012, 05:52 PM   #1
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Patricia56's Avatar
Join Date: Jul 2012
Location: Northern California, USA

I just posted this in reply to a post in the Parent's Forum. Thought I would also post it here FYI. If you see thing differently or have greater expertise in this stuff and feel I have mis-stated something, please reply or PM me. Thanks, Patricia

HSTCL update

This is a very long post that has four parts to it. As always, talk with your doctor about your concerns. Pin them to the wall if necessary to get the best answers they can give you on the latest research/findings/risk assessments.

The four parts:

• At the beginning are summaries/comments on two very recently published papers about HSTCL (hepatosplenic t-cell lymphoma). .
• My attempt to put HSTCL in context or describe the big picture. If someone else knows more about interpreting/understanding epidemiological data like this, I hope you will share/comment.
• HSTCL prognosis and treatment.
• My 2 cents FWIW.

1) Recent research studies:

Study #1 - http://www.ncbi.nlm.nih.gov/pubmed/21823196

The incidence of hepatosplenic T-cell lymphoma in a large managed care organization, with reference to anti-tumornecrosis factor therapy, Northern California, 2000-2006.

The researchers found 6 cases of HSTCL diagnosed at Kaiser Northern California from 2000-2006. 1 case was Crohn’s (steroids, thiopurine and remicade) and 1 was HIV-related. There is no info on the other 4. They calculated an annual age-standardized incidence rate of 0.3 (95%CI, 0.11-0.65) per million person-years.

It is hard to know exactly what this means for children with IBD who are taking biologics or immune suppressant meds. What it does show is that the frequency of this kind of cancer in the general population is very, very rare. This makes it pretty much impossible for anyone to estimate the risk of developing HSTCL in youth with IBD. For comparison, the estimated annual age standardized incidence rate in 2008 for Non-Hodgkin’s Lymphoma in the US was 10.2 per million person-years.

Study #2 - http://www.ncbi.nlm.nih.gov/pubmed/21941193

Hepatosplenic T-cell lymphoma in patients receiving TNF-α inhibitor therapy: expanding the groups at risk.

The study authors say three more groups should be considered at higher risk for HSTCL including women, rheumatoid arthritis (RA) patients, and age 65+. This analysis is based on the 25 cases reported to the FDA. I only had access to the abstract which does not contain enough info to truly evaluate these conclusions.

I am skeptical that they had enough data to justify the recommendations. For example, 22 cases had IBD and only 3 had RA. Ok, you can say 3 had RA so people with RA are at risk. There is pretty good evidence that people with RA and high rates of inflammation are already at a very high risk for lymphomas (perhaps as much as 25 times higher than general population). Maybe some of those people would have gotten HSTCL anyway. At what point do you ring the alarm bell for RA patients? 1 case, 2 cases, 3 cases out of hundreds of thousands of patients on immunomodulators and/or biologics?

2. Context:
• Both of these papers are based on adults, not youth/young adults/kids making it difficult to know to what extent these findings apply to our kids.
• How many people are taking these meds who therefore could be at risk of HSTCL? The potential total number of people who have used these meds is 2.4 million+.Abbott labs says 500,000 people worldwide have used or are currently on Humira. Remicade is estimated at 1.3 million people, Enbrel 600,000 and of course much fewer for Cimzia and a couple other new or rarely used TNF-alpha blockers. That means There are no separate figures for children so I assume they are included in these numbers. There are no separate reported figures that I could find for IBD vs. RA and other diseases so these all seem to have been lumped together.
• It is absolutely impossible to know how many people are now taking or have taken immunomodulators(Mercaptopurine and Methotrexate). These drugs are widely used for other conditions like cancer treatment. Mercaptopurine and variants have been used to treat IBD for more than 30 years. I think it is safe to say that the number of people who have used these meds may be 10 times the number of people who have taken a TNF-alpha blocker.

3. HSTCL prognosis and treatment

None of this matters if it is your child that gets HSTCL since prognosis is “very grim”. Of the 25 cases reported to FDA one went into remission and the rest died with median survival of 8 months. I found 3 case reports of remission following intensive chemotherapy in anyone with HSTCL. The most recent case report advocated consideration of a new treatment strategy based on viewing this cancer as a blood-based cancer like leukemia instead of a lymphoma (immune system).

4. My 2 cents

For our family it came down to choosing between:
• potential unknown risk of HSTCL (which seems very tiny to me)
• the well-known high risk of IBD complications and long term damage from uncontrolled IBD plus current quality of life issues. My son’s doctor says there’s no actual risk. Rather he is certain that these kids will get sicker without these kinds of treatment.

Before Mercaptopurine (6-MP, Imuran, etc.) became available and widely used to treat IBD the rates of surgery were sky high. Within 10 years of diagnosis upwards of 70% of IBDers had required abdominal surgery. Many spent years on prednisone. Many were unable to work or life anything like a normal life. The life expectancy of people with IBD was estimated to be as much as 20 years less than average people. I for one don’t want to go back to those days.

On the one hand I hate having to make these kinds of decisions. On the other hand I am thankful that I have the luxury of choice. Some parents can only stand by and watch their child suffer and/or die because no treatment is possible or available for their child’s condition or disease.


Badger, 18, CD, overall great guy
Dxd age 10, 2006 after nearly 1 year of active sx
Current CD meds: Remicade, Methotrexate and Omeprazole, Vit. D, Calcium, Folic Acid, Probiotic

Nothing I say here should be construed as medical advice. I am not a doctor. These are just my opinions.
12-08-2014, 11:34 PM   #2
Join Date: Dec 2014
Location: Israel
lots of important information for me, thank you
12-10-2014, 10:13 PM   #3
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Join Date: Jul 2014
Location: Ontario

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I recently noted that the CCFC posted the surgical rate for Crohn's patients is now 47%. That is a huge difference from the 70% that you noted above - pre-thiopurine drugs. 70% was also the number I read in the books we were given by the hospital when our daughter was diagnosed.

I wonder if the number 47% takes into account Biologics or if they are too new to put a number on for a lifetime disease related surgery rate.

Anyway, as a parent with a young child who has been recently diagnosed, I appreciate your breakdown of the relative risks. Thank you for taking the time to post it.
Mom to daughter,age 7, diagnosed at age 3 with Crohn's Disease and son, age 9, diagnosed at age 9 with Crohn's Disease

Current Treatment: Daughter - 40mg weekly Humira,
10mg oral Methotrexate, iron, zinc, Vitamin D.

Son - 20mg Methotrexate injections, 8 weeks EEN
12-10-2014, 10:37 PM   #4
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Location: Georgia

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It seems there was a recent study suggesting the use of biologics early in, after dx, does affect the risk of surgery in a positive way. The paper may be in the parents of kids research thread.
Mom to
C age 19
dx March 2012 CD

CURRENT MEDS: MTX injections, Stelara

Dx May 2014: JSpA
8/2014 ileocecectomy
9/2017 G tube

PAST MEDS: remicade, oral mtx, humira
12-10-2014, 10:47 PM   #5
my little penguin
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The researchers evaluated data from 552 patients who participated in the trial RISK between 2008 and 2012. They used propensity score matching "to avoid the usual problem of confounding by indication when using observational cohort data to explore differences in treatment response." More than half of the patients (61%) were male, their mean age was 11.8 years, and 63% had a Pediatric Crohn’s Disease Activity Index (PCDAI) score of greater than 30. The primary outcome of interest was corticosteroid-free clinical remission (defined as a PCDAI of 10 or less) at 1 year after diagnosis without luminal resection (Gastroenterology 2013 [doi: 10.1053/j.gastro.2013.10.027]).


And from the peds teaserch section here
Same paper Plus other

DS - -Crohn's -Stelara -mtx

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