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ACUTE MYELOID LEUKEMIA

Infectious complications after intensive chemotherapy with CLAG-M versus 7+3 for AML and other high-grade myeloid neoplasms

Leukemia volume 37, pages 298–307 (2023)Cite this article

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Abstract

Contemporary data on infections after intensive chemotherapy for acute myeloid leukemia (AML) are scarce. Cladribine, high-dose cytarabine, G-CSF, and dose-escalated mitoxantrone (“CLAG-M”) may result in higher remission rates than standard-dose cytarabine plus anthracycline (“7 + 3”) but may result in more infections. We compared moderate to severe infections occurring up to 90 days after the first induction cycle for AML or other high-grade myeloid neoplasms in patients receiving CLAG-M for newly diagnosed (n = 196) or relapsed/refractory disease (n = 131) or 7 + 3 for newly diagnosed disease (n = 115). For newly diagnosed disease, microbiologically documented infections were more frequent after CLAG-M compared to 7 + 3 (adjusted rate ratio, 1.65 [95% CI, 1.06–2.58]; P = 0.03), with a cumulative incidence of 27.8% and 16.5% by day 90, respectively. Patients receiving CLAG-M for relapsed/refractory disease had the highest cumulative incidence of 50.7%. Bacterial bloodstream infections were the most frequent followed by respiratory tract infections. Among 29 patients (7%) who died, infection was a primary or contributing cause of death in 59%. These data indicate that infections continue to cause substantial morbidity in patients treated for AML, especially those treated for relapsed/refractory disease, and are more common with newer, more myelosuppressive regimens such as CLAG-M. Improved strategies for infection prevention are needed.

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Fig. 1: Cumulative incidence curves of time-to-first moderate to severe microbiologically documented infection after start of chemotherapy.
Fig. 2: Infection incidence rates.
Fig. 3: Cumulative incidence curves of time-to-first proven or probable invasive fungal infection by receipt of mold-active prophylaxis.
Fig. 4: Anatomical site and characteristics of infections.

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Data availability

The datasets generated and analyzed for this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by a grant from Nohla Therapeutics (now Deverra Therapeutics).

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Authors and Affiliations

  1. Fred Hutchinson Cancer Center, Seattle, WA, USA

    Carla S. Walti, Anna B. Halpern, Hu Xie, Erika S. Kiem, E. Lisa Chung, Emily M. Huebner, Colleen Delaney, Catherine Liu, Steven A. Pergam, Guang-Shing Cheng, Louise E. Kimball, Wendy M. Leisenring, Michael Boeckh, Roland B. Walter & Joshua A. Hill

  2. University of Washington, Seattle, WA, USA

    Anna B. Halpern, Kelda G. Schonhoff, Catherine Liu, Steven A. Pergam, Guang-Shing Cheng, Michael Boeckh, Roland B. Walter & Joshua A. Hill

  3. Deverra Therapeutics, Seattle, WA, USA

    Colleen Delaney

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Contributions

JAH, RBW, ABH, and CSW designed the study and interpreted the results; HX, WML, CSW, and JAH analyzed the data and created the figures; ABH, ELC, EMH, LEK, CSW, ESK, and JAH collected data; CSW and JAH drafted the manuscript; and ABH, HX, ESK, ELC, KMG, EMH, CD, CL, SAP, G-SC, LEK, WML, MB, and RBW contributed to the writing and revision of the manuscript and approved the final version.

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Correspondence to Joshua A. Hill.

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Competing interests

JAH received a research grant from Deverra Therapeutics (formerly Nohla Therapeutics) for support of the work. No other author received any support for the current work. CSW, HX, ESK, ELC, KMG, EMH, CL, LEK, and WML have nothing to disclose. ABH served as a consultant for Abvie and Agios and received research funding from Pfizer, Nohla Therapeutics, Jazz Pharmaceuticals, Imago Pharmaceuticals, Novartis, Bayer, Tolero Pharmaceuticals, Agios Pharmaceuticals, and Gilead. CD is scientific founder and CSO of Deverra Therapeutics. SAP received research funding from Chimerix, Inc., Global Life Technologies, Inc., Merck & Co., and participated in an NIH clinical trial where vaccines were provided by Sanofi Aventis. GSC served as a consultant to Janssen Pharmaceuticals. MB served as a consultant for AlloVir, Gilead, Merck, SymBio Pharmaceuticals, Vir Biotechnolgy, Helocyte (also options to acquire ownership interest), Evrys Bio (also options to acquire ownership interest), and GSK, and received research funding from Gilead, GSK, Janssen, Ansun Biopharma, Vir Biotechnology and Merck. RBW received laboratory research grants and/or clinical trial support from Agios, Amgen, Aptevo, Arog, BioLineRx, Celgene, ImmunoGen, Janssen, Jazz, Kura, MacroGenics, Pfizer, Selvita, and Stemline; has ownership interests in Amphivena; and is (or has been) a consultant to Agios, Amgen, Amphivena, Aptevo, Astellas, BioLineRx, Boston Biomedical, Bristol Myers Squibb, Celgene, Genentech, GlaxoSmithKline, Janssen, Jazz, Kite, Kronos, MacroGenics, New Link Genetics, Pfizer, and Race. JAH served as a consultant for Gilead, Amplyx, AlloVir, Allogene therapeutics, CRISPR therapeutics, CLS Behring, PtumHealth, Octapharma, and Takeda, and received research funding from Gilead, AlloVir, and Takeda.

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Walti, C.S., Halpern, A.B., Xie, H. et al. Infectious complications after intensive chemotherapy with CLAG-M versus 7+3 for AML and other high-grade myeloid neoplasms. Leukemia 37, 298–307 (2023). https://doi.org/10.1038/s41375-022-01786-9

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