Data
We conducted a retrospective review of patients diagnosed with AML at our institution from 12/1/2016 until 7/1/2020 and who received either decitabine or azacitidine in combination with venetoclax.
Patient Population
We included patients aged 18 and older who received the above therapies at any point in their illness, frontline for newly diagnosed disease or as salvage therapy for relapse or refractory leukemia. We stratified patients based on whether venetoclax was initiated in the inpatient or outpatient setting.
Outcomes
We examined baseline AML characteristics including initial white blood cell count, blast count, cytogenetics and molecular profiles as well as baseline TLS markers (potassium, calcium, phosphate, uric acid, and creatinine) prior to the initiation of venetoclax. Using the Cairo-Bishop Criteria as modified by Howard we examined the number of episodes of laboratory or clinical tumor lysis in all patients [14].
TLS as defined by the Cairo-Bishop Criteria as modified by Howard is stratified into laboratory and clinical tumor lysis. Laboratory tumor lysis is defined as having at least two of four alterations in serum electrolyte or uric acid values during the same 24-hour period in the 3 days prior to or up to 7 days following treatment of a malignancy. These are: 1) Uric Acid level of >8.0 mg/dl 2) Phosphorous >4.5 mg/dl 3) Potassium >6.0 mmol/liter and 4) Corrected calcium of <9.0 mg/dl or ionized calcium <4.5 mg/dl. Acute kidney injury is not an aspect of laboratory TLS.
Clinical TLS is defined as the presence of laboratory tumor lysis in addition to one of 3 clinical scenarios. These are: 1) Cardiac dysrhythmia or sudden death felt likely or definitely to be caused by hyperkalemia or hypocalcemia 2) Seizure, neuromuscular irritability, hypotension, or heart failure felt likely or definitely to have been caused by hypocalcemia and 3) Acute kidney injury as defined by an increase in serum creatinine of 0.3mg/dl or if no baseline value is present than a value of >1.5 times the upper limit of normal, or oliguria defined as <0.5ml/kg/hr of urine output over 6 hours.
Baseline TLS labs in our study were collected in all patients. As the majority of patients had initiation of venetoclax in the outpatient setting many did not have values within 3 days of starting treatment. In these patients the values most recently obtained prior to initiating venetoclax were used as baseline values. Similarly, not all patients had lab values obtained within 1 week of starting venetoclax. For the purpose of this study it was assumed these patients did not have laboratory or clinical tumor lysis. Thirty-day mortality from initiation of venetoclax was measured to account for possible unidentified episodes of clinical tumor lysis.
As noted above laboratory tumor lysis requires the presence of at least two lab abnormalities. We additionally made note of patients with only one lab abnormality to broaden our analysis to include patients who may have been at risk of developing but did not meet criteria of laboratory or clinical tumor lysis.
Statistical Methods
Fisher's exact test and Wilcoxon rank-sum tests were performed to examine differences in categorical and continuous variables.
IRB Approval
This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Human Investigation Committee (IRB) of Rhode Island Hospital approved this study.