Factors predicting response and graft-versus-host disease after donor lymphocyte infusions: a study on 593 infusions

In the present study, we analyze factors predicting graft-versus-host disease (GvHD) and response after donor lymphocyte infusions (DLI). A total of 100 patients received 593 DLI between June 1990 and December 2000 in a bulk dose (n =14) or in escalating dose infusions (n = 86). Patients were analyzed after stratification for type of relapse: (1) molecular relapse (n=6), (2) cytogenetic relapse (n = 20), (3) chronic phase of chronic myeloid leukemia (CML) or complete remission of other disease post chemotherapy (n = 24), (4) CML in accelerated/blastic phase (n =14), (5) resistant disease not responding to chemotherapy (n = 36). The proportion of responders to DLI in these five groups was 100, 90, 75, 36 and 0% (P<0.0001). Factors predicting response by multivariate analysis were type of relapse (P<0.0001), post-DLI GvHD (P=0.005), pancytopenia (P=0.008), and a diagnosis of CML (P=0.04). Acute GvHD (grades II-IV) occurred in 21 patients (21%), and correlated in multivariate analysis with pancytopenia and less than four DLI. Other predictors of GvHD were the number of CD3+ cells/infusion and serum levels of gamma-glutamyl transferase (gammaGT). The actuarial probability of treatment-related mortality was 9% for HLA identical siblings and 44% for alternative donor transplants (P=0.006). Response to DLI is predicted by tumor burden and is associated with GvHD and pancytopenia.