DONOR LYMPHOCYTE INFUSIONS (DLI): Risk Factors for Non Relapse Mortality (NRM) In 287 Patients Receiving DLI

Donor lymphocyte infusions (DLI) have been now used for 20 years in patients undergoing allogeneic hemopoietic stem cells transplants (HSCT). Initially DLI were only used in patients with chronic myeloid leukemia (CML) for the treatment of relapse. Subsequently DLI have been used in other disorders, and for different reasons, such as molecular relapse, mixed chimerism and also in prophylaxis programs.

DLI are associate with a risk of Graft versus Host Disease (GvHD) and non relapse mortality (NRM). We have been using escalating doses of DLI for many years, and wanted to assess risk factors for GvHD and NRM.

We analyzed 287 patients who received a total of 1288 DLI, for different reasons and at different intervals from transplant. The median number of DLI was 4 (1-15) the median interval between transplant and DLi was 282 dasy (1-4480), the median number of infused CD3 cells /kg of recipients body weight was 1×10^7 (1×10^3- 5×10^7). The diagnoses were chronic myeloid leukemia (n=78), acute leukemia (n=100), myelofibrosis (n=21), myelodisplastic syndrome (n=14), lymphoma (n= 35), other diagnosis (n=38). Median patients age was 40 (12-68).

Statistical analysis. Factors studied for an association with GvHD and NRM were donor type (siblings/alternative donors), diagbnosis (CML others), year of DLI (</> 2001), maximum dose of DLI (</> 1×10^7), recipient age (<=/>40 years), donor age (<=/> 40 years), number of DLI (</> 4), interval transplant-DLI (</> 282 days), phase of the disease at transplant (early/advanced), and gender (donor recipient).

Seventy patients (24%) developed acute GvHD grade II-IV. In univariate analysis we coujld only identify the year of transplant as a predictor: GvHD II-IV developed in 29% of patients grafted before 2001 and in 19% of patients grafted later (p=0.04). In multivariate analysis this result was confirmed.

With a median follow up for surviving patients of 2346 days (125-7194) 158 patients survive (55%). The primary cause of death was relapse of the original disease in 100 patients (35%), whereas 29 died of NRM (10%).

Factors predicting NRM in univariate analysis were interval diagnosis-DLI, donor type and patient age. In multivariate COX analysis, the strongest predictor for NRM was the interval between transplant and DLI (p=00001) with a RR of 6.6 of NMR for patients receiving DLI before the median intgerval (282 days). Other predictors were donor type (siblings had a risk of 0.43, p=0.04), patients age (with a risk of 2.3 for patients over the age of 40) and advanced disease at the time of transplant (p=0.01)

In this relatively large series of consecutive DLI, the risk of acute GvHD was relatively low, and we could not identify significant predictors. NRM was strongly associated with the interval between transplant and DLI, and this may be a warning for strategies aimed at improving GvL in patients with advanced leukemia, with very early administration of DLI.

No relevant conflicts of interest to declare.