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. 2025 Apr;114(4):626-635.
doi: 10.1111/ejh.14371. Epub 2024 Dec 26.

Tumor Lysis Syndrome in Acute Myeloid Leukemia Patients Treated With a Venetoclax Based Regimen

Margaret Rowe  1 , Daria Babushok  2 , Martin Carroll  2 , Alison Carulli  2 , Noelle Frey  2 , Saar Gill  2 , Elizabeth Hexner  2 , Rebecca Hirsh  2 , Nasheed Hossain  2 , Catherine Lai  2 , Alison Loren  2 , Selina Luger  2 , Ivan Maillard  2 , Shannon McCurdy  2 , Andrew Matthews  2 , Mary Ellen Martin  2 , Vikram R Paralkar  2 , Alexander Perl  2 , David Porter  2 , Keith Pratz  2 , Edward Stadtmauer  2 , Ximena Jordan Bruno  2
Affiliations

Tumor Lysis Syndrome in Acute Myeloid Leukemia Patients Treated With a Venetoclax Based Regimen

Margaret Rowe et al. Eur J Haematol. 2025 Apr.

Abstract

Venetoclax with hypomethylating agents (HMA) is the standard of care for acute myeloid leukemia (AML) in patients ineligible for intensive chemotherapy and is associated with tumor lysis syndrome (TLS). TLS prophylaxis and the use of Cairo Bishop versus Howard diagnostic criteria are not standardized. Here we report TLS prophylaxis and incidence in a retrospective cohort of 100 consecutive AML patients treated with venetoclax and HMA. Thirty four patients developed laboratory Cairo Bishop TLS; 8 of these met criteria for clinical Cairo Bishop TLS. Only 6 of patients met Howard TLS criteria. Fourteen patients had spontaneous TLS. Ninety two out of 100 patients had a white blood cell count (WBC) < 25 000 cells/μL at treatment start. Prophylaxis like the original venetoclax trial with allopurinol (56%), intravenous fluids (21%), and frequent lab monitoring (56%) was less common. There was a trend toward increased Cairo Bishop TLS in patients with WBC ≥ 15 000 cells/μL. In our study Howard TLS criteria better identified patients with significant TLS. Aggressive TLS prophylaxis was uncommon in our cohort and is likely unnecessary for most patients at low risk of TLS.

Keywords: Leukoreduction; Venetoclax; acute myeloid leukemia; prophylaxis; tumor lysis syndrome.

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Conflict of interest statement

MR, DB, EH, RH, NH, AL, SM, AM, MEM, VRP: None. MC: Cartography Bioscences: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals: Consultancy. NF: Kite Pharma: Consultancy; Sana Biotechnology: Consultancy. SG: Kite Pharma: Consultancy; Carisma Therapeutics: Current equity holder in publicly‐traded company, Current holder of stock options in a privately‐held company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: patents, Research Funding; Interius Biotherapeutics: Current equity holder in private company, Current holder of stock options in a privately‐held company, Membership on an entity's Board of Directors or advisory committees, Research Funding; Asher: Research Funding; Currus: Membership on an entity's Board of Directors or advisory committees; Inndura: Membership on an entity's Board of Directors or advisory committees; Mission Bio: Membership on an entity's Board of Directors or advisory committees; NKILT: Membership on an entity's Board of Directors or advisory committees; Vor Bio: Membership on an entity's Board of Directors or advisory committees, Research Funding. CL: Novartis: Consultancy; Rigel: Consultancy; Astellas: Consultancy; AbbVie: Consultancy; BMS: Consultancy; Genentech: Consultancy; Daiichi: Consultancy; Taiho: Consultancy; Pfizer: Consultancy; Jazz: Consultancy, Research Funding. SL: Onconova: Research Funding; Bristol‐Myers Squibb: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Marker Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Astellas: Honoraria. IM: Garuda Therapeutics: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Regeneron: Research Funding. AP: Forma: Consultancy; Rigel: Honoraria; Actinium: Honoraria; Aptose: Honoraria; BerGen Bio: Honoraria; Genentech: Honoraria; Foghorn: Consultancy; FujiFilm: Research Funding; Syndax: Research Funding; Immunogen: Honoraria; BMS: Honoraria; Beat AML: Other: Participation on a Data Safety Monitoring Board or Advisory Board; Bayer: Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi‐Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. DP: Sana Therapeutics: Consultancy, Current equity holder in publicly‐traded company; Tmunity: Patents & Royalties; Wiley and Sons Publishing: Honoraria; Novartis: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Mirror Biologics: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Genentech: Current equity holder in publicly‐traded company; DeCart: Membership on an entity's Board of Directors or advisory committees; Capstan Bio: Honoraria; BMS: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Angiocrine Bio: Membership on an entity's Board of Directors or advisory committees. KP: Roche: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Jazz Pharamceuticals: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Bristol‐Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Research Funding; AbbVie: Consultancy, Research Funding. ES: Amgen: Consultancy; Janssen: Consultancy; BMS: Consultancy; Abbvie: Consultancy, Research Funding; genmab: Consultancy.

Figures

FIGURE 1
FIGURE 1
TLS subtypes. All patients with clinical TLS had acute kidney injury. CB‐TLS, Cairo Bishop TLS; H‐TLS, Howard TLS.
FIGURE 2
FIGURE 2
Timing of TLS onset. 4 patients who experienced TLS spontaneously and after starting venetoclax are counted at both time points. 3 patients whose lab abnormalities were attributed to another pathology are excluded from this graph. CB‐TLS, Cairo Bishop TLS; H‐TLS, Howard TLS.
FIGURE 3
FIGURE 3
Forest plot showing relative risk (RR) with 95% confidence interval (CI) for Cairo‐Bishop TLS.
FIGURE 4
FIGURE 4
TLS significance as defined by requiring hospitalization (if started treatment outpatient) or ICU transfer, receiving rasburicase, developing an AKI, or having treatment held due to TLS. *Six of these patients met laboratory or clinical Howard criteria at the onset of their spontaneous TLS. Their laboratory abnormalities were not as severe by ≤ 3 days prior to venetoclax start when the formal time frame for defining TLS begins. CB‐TLS, Cairo Bishop TLS; H‐TLS, Howard TLS.
FIGURE 5
FIGURE 5
Proposed algorithm for identifying patients at increased risk of significant TLS. Images from www.flaticon.com.
See this image and copyright information in PMC

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