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Immortal time bias in hematopoietic cell transplantation

Bone Marrow Transplantation volume 58, page 946 (2023)Cite this article

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We read with interest the study by Fan et al. [1]. They have compared patients who have received decitabine maintenance with those who have not in patients with acute lymphoblastic leukemia following hematopoietic cell transplantation.

When the patients’ trajectories begin, we are unaware whether the patients will receive decitabine or not because that shall happen in the future. However, in their analyses, patients who started decitabine were treated as if they had always received decitabine. This is a classic example of immortal time bias [2]. Immortal time bias arises when a patient receives a treatment during his journey but is treated in the analyses as always receiving the treatment. Since this patient cannot have relapsed or died to receive the treatment (decitabine), i.e., must be alive and in remission, this patient is deemed “immortal” for a period of time. Median time of transplantation to decitabine maintenance in the Fan et al study was 89 days, which is a long time not to account for.

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References

  1. Fan J, Lu R, Zhu J, Guo X, Wan D, Xie X, et al. Effects of post-transplant maintenance therapy with decitabine prophylaxis on the relapse for acute lymphoblastic leukemia. Bone Marrow Transplant. 2023. https://doi.org/10.1038/s41409-023-01948-y.

  2. Christensen DM, Gislason G, Gerds T. Matters Arising: Immortal time bias in the analysis of drug prescription trajectories. npj Digit Med. 2022;5:190.

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  3. Therneau T, Crowson C, Atkinson E. Using time dependent covariates and time dependent coefficients in the Cox Model. 2023. https://cran.r-project.org/web/packages/survival/vignettes/timedep.pdf. Accessed Mar 2023.

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  1. Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo, Brazil

    Leonardo Javier Arcuri

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  1. Leonardo Javier Arcuri
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Correspondence to Leonardo Javier Arcuri.

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Arcuri, L.J. Immortal time bias in hematopoietic cell transplantation. Bone Marrow Transplant 58, 946 (2023). https://doi.org/10.1038/s41409-023-01994-6

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