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Dose intensity and the toxicity and efficacy of allogeneic hematopoietic cell transplantation

Leukemia volume 19, pages 171–175 (2005)Cite this article

The intensity of the preparative regimen contributes to the overall toxicity and antitumor efficacy of allogeneic hematopoietic cell transplantation (HCT). However, other factors, principally graft-versus-host disease (GVHD) and its treatment, cause toxicity, and the graft-versus-tumor (GVT) effect of allogeneic transplantation is a key component of its efficacy. With the goal of developing an idealized preparative regimen, understanding the contribution of dose intensity to both the unfavorable and favorable outcomes of transplantation is important. However, in the past, it has been difficult to accurately determine the impact of dose on toxicity and efficacy because the majority of the preparative regimens in use were of similar intensity given the perceived need for a near-ablative dose of therapy to achieve engraftment. More recently, preclinical studies have shown that allogeneic engraftment can be achieved with relatively nontoxic approaches and the power of the GVT effect has been better appreciated. With these two advances, less-intensive preparative regimens have been developed and tested in large numbers of patients. This experience now allows a better understanding of the contributions of dose to the toxicity and efficacy of allogeneic HCT.

The fact that allogeneic engraftment can be achieved without myeloablation has been understood essentially since allogeneic transplantation was first achieved in humans. The very first successful allogeneic transplants for aplastic anemia were achieved following a conditioning regimen of 50 mg/kg cyclophosphamide on each of four consecutive days, a dose that was known to be less than myeloablative.1 One of the earliest regimens used for successful allogeneic transplantation in leukemia, along with the now famous cyclophosphamide/total body radiation (Cy/TBI) and busulfan/cyclophosphamide (Bu/Cy) regimens, was the BACT regimen, which combined BCNU with cytarabine, 6-thioguanine and cyclophosphamide. This same regimen was used without marrow support in the control arm of the first comparative study demonstrating the utility of cryopreserved autologous marrow, and full recovery was seen without marrow support, albeit after over 3 weeks of marrow aplasia.2

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Acknowledgements

This work was supported, in part, by grants CA 18029, CA 15704, CA 78902, and HL 36444 from the National Institutes of Health, DHHS.

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  1. Fred Hutchinson Cancer Research Center and University of Washington School of Medicine, Seattle, WA, USA

    F R Appelbaum

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Correspondence to F R Appelbaum.

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This paper is part of a series of keynote addresses to be published in Leukemia. They were presented at the Acute Leukemia Forum, San Francisco, Friday April 16, 2004

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Appelbaum, F. Dose intensity and the toxicity and efficacy of allogeneic hematopoietic cell transplantation. Leukemia 19, 171–175 (2005). https://doi.org/10.1038/sj.leu.2403609

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