Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2024 May;29(5):535-544.
doi: 10.1007/s10147-023-02465-0. Epub 2024 Mar 18.

Effectiveness and safety of primary prophylaxis with G-CSF after induction therapy for acute myeloid leukemia: a systematic review and meta-analysis of the clinical practice guidelines for the use of G-CSF 2022 from the Japan society of clinical oncology

Tomoya Maeda  1 , Yuho Najima  2 , Yutaro Kamiyama  3 , Shinji Nakao  4 , Yukinori Ozaki  5 , Hiroshi Nishio  6 , Kenji Tsuchihashi  7 , Eiki Ichihara  8 , Yuji Miumra  9 , Makoto Endo  10 , Dai Maruyama  11 , Tatsuhiro Yoshinami  12 , Nobuyuki Susumu  13 , Munetaka Takekuma  14 , Takashi Motohashi  15 , Mamoru Ito  7 , Eishi Baba  16 , Nobuaki Ochi  17 , Toshio Kubo  18 , Keita Uchino  19 , Takahiro Kimura  20 , Shinobu Tamura  21 , Hitomi Nishimoto  22 , Yasuhisa Kato  23 , Atsushi Sato  24 , Toshimi Takano  5 , Shingo Yano  3
Affiliations
Meta-Analysis

Effectiveness and safety of primary prophylaxis with G-CSF after induction therapy for acute myeloid leukemia: a systematic review and meta-analysis of the clinical practice guidelines for the use of G-CSF 2022 from the Japan society of clinical oncology

Tomoya Maeda et al. Int J Clin Oncol. 2024 May.

Abstract

Although granulocyte colony-stimulating factor (G-CSF) reduces the incidence, duration, and severity of neutropenia, its prophylactic use for acute myeloid leukemia (AML) remains controversial due to a theoretically increased risk of relapse. The present study investigated the effects of G-CSF as primary prophylaxis for AML with remission induction therapy. A detailed literature search for related studies was performed using PubMed, Ichushi-Web, and the Cochrane Library. Data were independently extracted and assessed by two reviewers. A qualitative analysis of pooled data was conducted, and the risk ratio with corresponding confidence intervals was calculated in the meta-analysis and summarized. Sixteen studies were included in the qualitative analysis, nine of which were examined in the meta-analysis. Although G-CSF significantly shortened the duration of neutropenia, primary prophylaxis with G-CSF did not correlate with infection-related mortality. Moreover, primary prophylaxis with G-CSF did not affect disease progression/recurrence, overall survival, or adverse events, such as musculoskeletal pain. However, evidence to support or discourage the use of G-CSF as primary prophylaxis for adult AML patients with induction therapy remains limited. Therefore, the use of G-CSF as primary prophylaxis can be considered for adult AML patients with remission induction therapy who are at a high risk of infectious complications.

Keywords: AML; Adults; G-CSF; Induction therapy; Meta-analysis; Neutropenia.

PubMed Disclaimer

Conflict of interest statement

TMa received research funding from Chugai. SN received honoraria from Kyowa Kirin. YO received honoraria from Daiichi Sankyo, Pfizer, Chugai, Eli Lilly, and Kyowa Kirin. KT received honoraria from Ono, Chugai, Taiho, and Novartis. EI received honoraria from Eli Lilly and research funding from MSD, Ono, Janssen, and Takeda. YM received honoraria from Ono, MSD, Takeda, Eisai, and Bristol Myers Squibb and research funding from MSD, Ono. DM received honoraria from Ono, Janssen, Nippon Shinyaku, Eisai, Mundi pharma, Kyowa Kirin, Chugai, Zenyaku, MSD, SymBio, Sanofi, AbbVie, Takeda, AstraZeneca, Bristol Myers Squibb, and Genmab and research funding from Amgen, Astellas, BioPharma, Novartis, Kyowa Kirin, Ono, Chugai, Janssen, Takeda, Otsuka, Sanofi, Bristol Myers Squibb, AbbVie, Eisai, MSD, Taiho, AstraZeneca, Eli Lilly, and Genmab. TY received honoraria from Kyowa Kirin, Pfizer, Chugai, Eli Lilly, MSD, AstraZeneca, and Eisai. TMo received honoraria from AstraZeneca, Chugai, and Myriad Genetics. EB received honoraria from Chugai, and Daiichi Sankyo and research funding from Taiho, and Chugai. TKu received honoraria from Chugai. TKi received honoraria from Sanofi. AS received honoraria from Chugai, and Taiho and scholarship donations Chugai, and Taiho. TT received honoraria from Daiichi Sankyo, Chugai, and Eli Lilly. SY received research funding from Otsuka. No other author has reported a potential conflict of interest relevant to this manuscript.

Figures

Fig. 1
Fig. 1
Modified PRISMA flow diagram of the literature search process. Each study was used in the meta-analysis of infection-related mortality (*1), disease progression/recurrence (*2), and adverse events, such as musculoskeletal pain (*3). PRISMA preferred reporting items for systematic reviews and meta-analysis
Fig. 2
Fig. 2
Infection-related mortality. (a) Forest plot and (b) funnel plot. A Forest plot and funnel plot of the risk ratio (RR) of infection-related mortality comparing granulocyte colony-stimulating factor (G-CSF) prophylaxis and control study arms for each study. The plot shows treatment effects versus the study size estimated from the standard error (SE) of log (RR). Open circles indicate individual studies in this meta-analysis. The broken line is a pseudo 95% confidence interval of effect measures in the study. A funnel plot showing the symmetrical distribution of studies indicating the absence of a publication bias. CI confidence interval, RR risk ratio, SE standard error
Fig. 3
Fig. 3
Disease progression/recurrence. (a) Forest plot and (b) funnel plot. A Forest plot and funnel plot of the risk ratio (RR) of disease progression/recurrence comparing granulocyte colony-stimulating factor (G-CSF) prophylaxis and control study arms for each study. There were too few studies and insufficient variations in standard errors to assess whether funnel plots were symmetric. However, there was no asymmetry visible in any of the funnel plots. CI confidence interval, RR risk ratio, SE standard error
Fig. 4
Fig. 4
Adverse events, such as musculoskeletal pain. (a) Forest plot and (b) funnel plot. A Forest plot and funnel plot of the risk ratio (RR) of adverse events, such as musculoskeletal pain, comparing granulocyte colony-stimulating factor (G-CSF) prophylaxis and control study arms for each study. Although there were too few studies and insufficient variations in standard errors (SE) to assess whether funnel plots were symmetric, there was no asymmetry visible in the funnel plots. CI confidence interval, RR risk ratio, SE standard error
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17–48. doi: 10.3322/caac.21763. - DOI - PubMed
    1. Peseski AM, McClean M, Green SD, et al. Management of fever and neutropenia in the adult patient with acute myeloid leukemia. Expert Rev Anti Infect Ther. 2021;19:359–378. doi: 10.1080/14787210.2020.1820863. - DOI - PubMed
    1. Ohno R, Tomonaga M, Kobayashi T, et al. Effect of granulocyte colony-stimulating factor after intensive induction therapy in relapsed or refractory acute leukemia. N Engl J Med. 1990;323:871–877. doi: 10.1056/NEJM199009273231304. - DOI - PubMed
    1. Avalos BR, Lazaryan A, Copelan EA. Can G-CSF cause leukemia in hematopoietic stem cell donors? Biol Blood Marrow Transplant. 2011;17:1739–1746. doi: 10.1016/j.bbmt.2011.07.003. - DOI - PubMed
    1. De Figueiredo LL, De Abreu e Lima RS, Rego EM. Granulocyte colony-stimulating factor and leukemogenesis. Mediators Inflamm. 2004;13:145–150. doi: 10.1080/09511920410001713574. - DOI - PMC - PubMed

MeSH terms

Substances