The risks of treatment.

[Kwenda]

The inherent risks of treatment.

Like all medical treatments the treatment of CLL does carry some risks. One of the aims of treatment is to remove / kill all the lymphocytic clones, and thus reduce the absolute white cell count. But the treatment has to also allow the body to naturally remove all the dead cells killed by the treatment.

If the dead cells are killed too quickly and are not removed fast enough then one can get TLS, or Tumor Lysis Syndrome.

This can be extremely serious or even life threatening, and thus we should be aware and read about TLS before any treatments

There is a link below which gives a good over view of TLS, and ‘Hairbear’ provided two additional links.

clinicaloptions.com/inPract...

pharmastrategyblog.com/2013...

cllsupport.healthunlocked.c...

Dick

[AussieNeil Partner Administrator]

Just goes to show you can have too much of a 'good' thing. Prior to the unfortunate deaths of a few brave ABT-199 trial patients (see third link), I don't think haematologists had seen TLS in CLL patients - no drugs were powerful enough to rapidly kill off lymphocytes in sufficient numbers to bring on TLS...

This is also another good reason to take extra good care of your liver and kidneys, so that they are better able to manage the extra demand placed on them of cleaning both the treatment drugs and the remnants of the killed lymphocytes out of your body before they poison you.

THE major challenge in finding successful chemotherapy treatments is finding something that will kill off cells that are almost, but not quite identical to healthy body cells, with minimal impact on healthy cells.

Neil

[HAIRBEAR_UK Founder Admin]

The late Professor Hamblin on "Side effects": mutated-unmuated.blogspot.c...

"Any effective treatment can cause tumor lysis syndrome (TLS). this means that release of toxins from the dying CLL cells are not cleared quickly enough and can damage or even kill the patient. The main toxins are potassium and uric acid. Prevention of TLS is by allopurinol for the uric acid and lots of fluids for the potassium."

Side Effects in easier language: mutated-unmuated.blogspot.c...

[AussieNeil Partner Administrator in reply to HAIRBEAR_UK]

I stand corrected thanks Nick!

From the parent posting link 2:

"TLS is most common in aggressive, fast growing (high grade) lymphomas and acute leukemias (e.g. ALL), but is less common in indolent disease such as chronic lymphocytic leukemia (CLL)."

A related posting to link 2 in the parent:

biotechstrategyblog.com/201...

includes:

"At the recent 2013 AACR annual meeting, Rod Humerickhouse, MD, PhD from AbbVie Global Pharma R&D ... told the AACR audience that Tumor Lysis Syndrome (TLS) adverse events occurred in 9 out of the 74 patients enrolled in three ABT-199 CLL clinical trials.

Two CLL trial participants died from TLS, and one had acute renal failure." (There were three trials suspended, two were for CLL and one for NHL patients.)

"Whether the tragic deaths should have been avoided we may never know, there remain unanswered questions as to whether the dose escalation was too aggressive, whether the risk of TLS was known, and if so whether patients were properly monitored."

The ABT-199 protocol now needs some adjustments to reduce the risk of TLS, arguably because ATB-199 is so effective.

From the parent posting link 2, TLS also happened on the CAR-T trials for CLL but was delayed until 20-50 days post infusion!

Chaya has more on how to prevent TLS:

updates.clltopics.org/278-p...

This just goes to show how the unlikely can still prove fatal on trials, why it is important to follow a careful expansion of trial recruits as more experience is gained with new treatment protocols and why risk reduces, but never disappears - even when the treatment becomes mainstream. Makes you appreciate how brave those entering trials - particularly in the early phases, really are and perhaps the older treatments less scary.

Neil

[AussieNeil Partner Administrator]

For those that are interested, there's a discussion on the CLL Forum about the ATB-199 trial recommencing which includes a member's experiences with TLS. One of the patients that died from TLS was a member of the CLL Forum and died within 48 hours of a dose escalation.

cllforum.com/forum63/10880....

(Note: you'll need to register to read the topic)