Lost father due to clinical TLS on day 1 of chemo with Aza-VEN
My 66-year-old father was diagnosed with AML on August 6. We were still awaiting the final subtype/molecular classification when he passed away on August 15. From diagnosis to his death was just 9 days. He had hypertension, was diabetic (no insulin, controlled through meds), and had a minor heart issue in 2004, but was cleared for chemo by the cardiologist.
His WBC was 44k at the time of diagnosis. He was given hydroxyurea, and his WBC had fallen to around 29k the day before treatment and may have been below 25k by the time treatment started. His platelets were around 18–19k before treatment, and he received a platelet transfusion after chemo. He also received medication for TLS/uric-acid prophylaxis.
He was admitted to start azacitidine + venetoclax (Aza-Ven). He was stable when admitted, apart from significant anxiety.
On day 1, the azacitidine infusion ran for roughly half an hour starting around 12:45 PM, and he took venetoclax at around 4 PM.
Within about 6 hours, he started deteriorating.
One of the most striking symptoms was extreme chills and violent shivering. The hospital room itself was already very warm, but he felt so intensely cold that we had to continuously hold a handheld heater close to him. He was still shivering despite that. He also developed nausea, severe restlessness, repeated bowel movements, and increasingly rapid/laboured breathing.
At one point he collapsed and briefly lost consciousness in the bathroom. He regained consciousness within seconds and was still communicating with us afterward.
Over the next couple of hours, his condition worsened dramatically. He became increasingly breathless and eventually suffered a cardiac arrest. CPR achieved ROSC and he was transferred to the ICU, but he later had another arrest/serious rhythm deterioration requiring shocks.
The doctors diagnosed clinical tumor lysis syndrome (TLS). His potassium was reportedly >9 mmol/L, his kidneys failed, and he developed multiorgan failure. He never regained consciousness after the initial arrest.
We ultimately withdrew life support after the ICU team told us that his chances of survival were extremely low and that meaningful neurological recovery, even if he survived, was unlikely.
His doctor told us that he has seen laboratory TLS during leukemia treatment but had personally never encountered a case of clinical TLS like this, and described what happened as an exceptionally rare event.
What is difficult for us to comprehend is the speed. He went from starting his first day of Aza-Ven to severe physiological deterioration and cardiac arrest within hours.
I understand that TLS is a known risk with venetoclax because rapid leukemia-cell death can release potassium and other intracellular contents into the bloodstream. But I am trying to understand how rare severe or fatal clinical TLS with Aza-Ven in AML actually is.
Has anyone here — patients, caregivers, hematologists/oncologists, nurses, etc. — experienced or witnessed severe clinical TLS after Aza-Ven, particularly cycle 1/day 1 and within only a few hours of treatment?
I'm not looking to blame his doctors or treatment team. I'm mainly trying to understand what happened to my father, how something this catastrophic could happen so rapidly, and whether anyone else has seen a similar case.
We thought we had at least some time ahead of us — hopefully months or longer, depending on his response to treatment. I never imagined that we would lose him on the first day of treatment to TLS.
None of us (on-duty doctor, nurses) understood that TLS was developing while these symptoms were happening. He was being treated in a regular hospital room rather than an ICU, and the deterioration happened incredibly quickly. By the time we understood how critically ill he was, he had suffered a cardiac arrest. He was completely fine until 2 hours before this death, i.e till 4.30 hours after he took venetoclax.
It has been incredibly difficult to process going from an AML diagnosis and planning his treatment to losing him only nine days later.
Context: 50mg ven, this was in India at one of the best hospitals. He was also asked to stop his blood thinners a few days prior to treatment.