T-Cell–Depleted Reduced-Intensity Conditioning Transplantation for Lymphoma: Do Donor Lymphocyte Infusions Really Matter?

Abstract

excellent contribution to the transplantation literature with the demonstration that T-cell– depleted transplantation can lead to prolonged survival in patients who have experienced multiple relapses of follicular lymphoma. The authors report a high response rate using donor lymphocyte infusions (DLI) with or without chemotherapy in patients who have experienced relapse after allogeneic transplantation. Using a similar regimen, we have observed frequent durable remissions and conversion to full donor chimerism after treatment with rituximab or nucleoside analogs even without DLI. 2 Thus, we concur with the high response rate for relapse, although the value of DLI versus other therapeutic modalities and the need for full donor chimerism for sustained remission requires additional study. A number of questions arise, however, regarding the authors’ recommendation to use DLI to prevent relapse in patients with mixed chimerism. In our experience with the use of similar conditioning regimens, mixed chimerism is quite common and varies in degree. 3 We and others have failed to find a relationship between the degree of mixed chimerism and risk for disease recurrence. 3,4 The authors state, “In the group given DLIs for MC [mixed chimerism] alone at 6 months, this effect was maintained, with patients converting to full donor status having a significant reduction in RR [relapse risk] compared with patients who exhibited persistent MC.” Statistical modeling of a variable that changes with time can be complicated. Additional details about the analysis would be useful, such as the degree and cellular compartment of mixed chimerism that prompted treatment, the chimerism time point(s) analyzed to predict relapse risk, and whether adjustments were made for time elapsed. We are unsure how patients with mixed donor chimerism after DLI can be combined in an analysis with patients who have mixed chimerism and never underwent DLI. If one does not use a single time point, the analysis would tend to show a benefit of DLI, given that those who remain alive without disease may receive additional DLI infusions to convert to full chimerism. In other words, lack of relapse may predict for full donor chimerism. Even if post-DLI mixed chimerism predicts for relapse, one does not know a priori who will achieve full donor chimerism with DLI; thus, such a result does not inform the decision to proceed with DLI. We advocate that prospective study of the risks and benefits of prophylactic DLI after alemtuzumab conditioning be undertaken. Until prospective studies are performed, the excellent results of salvage therapy with or without DLI at the time of relapse support salvage therapy rather than prophylactic DLI.