Dose intensity for conditioning in allogeneic hematopoietic cell transplantation: can we recommend when and for whom in 2021?

Allogeneic hematopoietic stem-cell transplantation is a potentially curative therapy for various hematologic diseases. An essential component of this procedure is the pre-transplant conditioning regimen, which should facilitate engraftment and reduce or eliminate tumor cells. The recognition of the substantial association of a graft-versus-tumor effect and the high toxicity of the commonly used conditioning regimen led to the introduction of more differentiated intensity strategies, with the aim of making hematopoietic stem-cell transplantation less toxic and safer, and thus more applicable to broader populations such as older or unfit patients. In general, prospective and retrospective studies suggest a correlation between increasing intensity and non relapse mortality and an inverse correlation with relapse incidence. In this review, we will summarize traditional and updated definitions for conditioning intensity strategies and the landscape of comparative prospective and retrospective studies, which may help to find the balance between the risk of non-relapse mortality and relapse. We will try to underscore the caveats regarding these definitions and analyses, by missing complex differences between intensity and toxicity as well as the broad influences of other factors in the transplantation procedure. We will summarize evidence regarding several confounders which may influence decisions when selecting the intensity of the conditioning regimen for any given patient, according to the individual risk of relapse and non-relapse mortality.

Automated summary

Allogeneic hematopoietic stem-cell transplantation is a potentially curative therapy for various hematologic diseases, with the success dependent on the conditioning regimen used pre-transplant. Studies have shown a correlation between conditioning regimen intensity and toxicity, prompting research to focus on reducing toxicity and increasing safety for broader populations. Individual factors and risks play a crucial role in selecting the appropriate intensity of the conditioning regimen.