Thank you very much for your comments. Drs Craddock and Grigg point out that T-cell depletion may not necessarily compromise donor stem cell engraftment in patients receiving reduced intensity conditioning regimens. They state rightfully that engraftment is dependent on donor–recipient tissue matching, T-cell content of the graft, intensity of the conditioning regimen, underlying disease and possibly stem cell dose, and that there is a complex interdependence of these variables. We agree that the high graft failure rate we observed pertains to the specific combination of these factors in our study. We had hypothesized that high stem cell doses may compensate for T-cell depletion in the setting we chose and unfortunately this was not so. In their correspondence they use the term in vivo T-cell depletion for antibodies such as Campath given as part of the conditioning regimen. We are not sure whether the so-called in vivo T-cell depletion and in vitro T-cell depletion should be used interchangeably. They furthermore argue that we did not use the purine analogue fludarabine as part of the conditioning regimen, and suggest that using fludarabine might have tipped the balance towards higher rates of engraftment. We are not sure whether the impact of using purine analogues is of such a magnitude. There are, to our knowledge, no comparative studies available at this time to support this notion. We agree with Drs Craddock and Grigg that several phase II studies using fludarabine as part of a reduced intensity conditioning regimen have reported high rates of engraftment.
Yours sincerely,
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