The regimen of busulafan. fludarabine and thymogen has been very quickly adopted and now studies of it as a base for adding additonal drugs have been initiated. However, there is room for caution. Thymoglobulin added to busulfan and fludarabine to conditioning before an allogeneic stem cell transplant may reduce the incidence and severity of graft versus host disease, especially in matched unrelated graft, but it can potentially promote higher reapse rates. In a retrospective review, Bredeson found exactly such an outcome. A recent study(McCune et al) confirmed low GVHD rates for this conditioning regimen and concluded: “The low rates of GvHD, particularly in its chronic form, were encouraging, and further biomarker studies are warranted to optimize the fludarabine/Tbusulfan/rATG conditioning regimen.” It stands to reason that mores studies on relapse rates should be performed before wide scale adoption of the addition of thymogen to busulfan-fludarabine.
A 2012 guideline (Fischmann et al) says this: “Our systematic review suggests that the addition of ATG during allogeneic HSCT significantly reduces the incidence of severe grades (II to IV) of acute GvHD, whereas the incidence of overall acute GVHD (grades I to IV) was not significantly lowered. This indicates a reduction of the severity but not the incidence of acute GVHD. However, this effect did not lead to a significant improvement of overall survival, which may be due to the severe potential side effects of the consecutively increased immunosuppression.Furthermore, future research is needed to clarify the effect of ATG on the incidence and severity of chronic GVHD and consequently on all aspects of quality of life.From the currently available data, no recommendation on the general use of ATG in allogeneic HSCT can be supported.
Bredeson CN, Zhang MJ, Agovi MA, Bacigalupo A, Bahlis NJ, Ballen K, Brown C, Chaudhry MA, Horowitz MM, Kurian S, Quinlan D, Muehlenbien CE, Russell JA, Savoie L, Rizzo JD, Stewart DA. Outcomes following HSCT using fludarabine, busulfan, and thymoglobulin: a matched comparison to allogeneic transplants conditioned with busulfan and cyclophosphamide.Biol Blood Marrow Transplant. 2008 Sep;14(9):993-1003.
Jeannine S. McCune, Erica L. Woodahl, Terry Furlong, Barry Storer, Joanne Wang, Shelly Heimfeld, H. Joachim Deeg and Paul V. O’Donnell, A pilot pharmacologic biomarker study of busulfan and fludarabine in hematopoietic cell transplant recipients Cancer Chemotherapy and Pharmacology Volume 69, Number 1 (2012), 263-272
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