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Venetoclax in combination with chemotherapy as treatment for pediatric advanced hematologic malignancies: A narrow therapeutic window of promise and peril
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  • Amanda E. Marinoff,
  • Kathryn Aaronson,
  • Anurag Agrawal,
  • Benjamin S. Braun,
  • Carla Golden,
  • Benjamin J. Huang,
  • Jennifer Michlitsch,
  • Erica Southworth,
  • Allyson Thrall,
  • Kieuhoa Vo,
  • Elliot Stieglitz
Amanda E. Marinoff
University of California San Francisco
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Kathryn Aaronson
University of California San Francisco
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Anurag Agrawal
University of California San Francisco
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Benjamin S. Braun
University of California San Francisco
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Carla Golden
University of California San Francisco
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Benjamin J. Huang
University of California San Francisco
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Jennifer Michlitsch
University of California San Francisco
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Erica Southworth
University of California San Francisco
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Allyson Thrall
University of California San Francisco
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Kieuhoa Vo
University of California San Francisco
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Elliot Stieglitz
University of California San Francisco

Corresponding Author:elliot.stieglitz@ucsf.edu

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Abstract

Background: V enetoclax is frequently used as salvage treatment in pediatric, adolescent, and young adult (AYA) patients with advanced hematologic malignancies. However, more robust data are needed from real-world studies to guide the safe and appropriate use of venetoclax in this population. Procedure: We retrospectively reviewed the medical records of all patients diagnosed with hematologic malignancies less than 30 years of age treated with venetoclax outside of clinical trials at the University of California San Francisco (UCSF) Benioff Children’s Hospitals from 2016 to 2022. Results: We identified 13 patients (AML , n= 8, B-ALL, n= 3, MDS, n= 2) aged 4 months to 27 years. A median of 3 prior lines of therapy were given (range 0 to 5). All patients received venetoclax in combination with either a hypomethylating agent or conventional chemotherapy. Three (23%) patients achieved a complete remission (CR); 2 (15%) achieved a partial remission (PR); 3 (23%) had stable disease (SD), and 5 (42%) had progressive disease. Median survival and time to progression from venetoclax initiation was 9 months (range 2.5 to 52 months), and 3 months (range 2 weeks to 7.5 months), respectively. Five patients (38%) developed life-threatening infections while receiving venetoclax, including bacteremia due to atypical organisms, invasive pulmonary infections with Aspergillus, cytomegalovirus (CMV) viremia, skin infections, encephalitis with bacterial brain abscesses. Conclusions: Venetoclax in combination with hypomethylating agents or cytotoxic chemotherapy was effective in a subset of pediatric/AYA patients with advanced hematologic malignancies, but was frequently associated with severe atypical infections, particularly in combination with cytotoxic chemotherapy.
19 Dec 2022Submission Checks Completed
19 Dec 2022Assigned to Editor
19 Dec 2022Submitted to Pediatric Blood & Cancer
19 Dec 2022Review(s) Completed, Editorial Evaluation Pending
19 Dec 2022Reviewer(s) Assigned
11 Jan 2023Editorial Decision: Revise Major
07 Mar 20231st Revision Received
07 Mar 2023Submission Checks Completed
07 Mar 2023Assigned to Editor
07 Mar 2023Review(s) Completed, Editorial Evaluation Pending
07 Mar 2023Reviewer(s) Assigned
13 Mar 2023Editorial Decision: Accept