Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?

Abstract

Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD. We retrospectively analyzed 500 patients treated with DLI for CML relapse (16% molecular, 30% cytogenetic, and 54% hematological) after alloSCT. The overall probabilities of failure- and secondary GVHD-free survival (FGFS) were 29% and 27% at 5 and 10 years after DLI, respectively. The type of relapse was the major factor influencing FGFS (40% for molecular and/or cytogenetic relapse and 20% for hematological relapse at 5 years, P < .001). Chronic GVHD before DLI and an interval <1 year between alloSCT and first DLI were independently associated with inferior FGFS in patients with molecular and/or cytogenetic relapse. Consequently, FGFS was 13%, 35%, to 56% at 5 years in patients with 2, 1, and 0 adverse features, respectively. In patients with hematological relapse, independent adverse prognostic factors for FGFS were initial dose of CD3(+) cells ≥ 50 × 10(6)/kg, donor-recipient sex mismatch, and chronic GVHD before DLI. FGFS was 0%, 17%, 33%, to 37% in patients with 3, 2, 1, and 0 adverse features, respectively. The probability of survival in remission without secondary GVHD was highest (>50% at 5 years) when DLI were given beyond 1 year from alloSCT for molecular and/or cytogenetic CML relapse that was not preceded by chronic GVHD.

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

“…These results have been collected by the European group for Blood and Marrow Transplantation (EBMT) (29), the US (26), and Japanese transplant centers (30). The best results with 70–80% cytogenetic complete remissions were reported for CML in cytogenetic and hematological relapse, other important factors being the presence of chronic GvHD prior to DLI and the time of relapse post-HSCT (31). Donor chimerism was also necessary for a successful GvL in CML.…”

“…CML relapse, molecular cytogenetic, or hematological has been reported as ranging from 16, 30, and 54%, respectively, using data from the Chronic Malignancies Working Party for the EBMT and based on 500 HSCT transplants from 1968 to 2004. The use of DLI in these cases was most successful if pre DLI factors such as chronic GvHD, cell dose, patient and donor gender mismatch, as previously described was taken into account (31). …”

Selective graft-versus-leukemia depends on magnitude and diversity of the alloreactive T cell response

“…Although the small sample size of our cohorts limited a reliable comparison, it is noteworthy that all patients with GVHD received DLI within the first year after alloSCT as compared with only 2 of 6 patients without GVHD. It was shown that the probability to survive without GVHD was highest if DLI was given 1 year or more after alloSCT (32,33). Early after alloSCT, higher levels of residual patient APCs may elicit higher response magnitudes.…”

Efficacy of Dasatinib in a CML Patient in Blast Crisis with F317L Mutation: A Case Report and Literature Review

“…Responses achieved after DLI are frequently durable, offering a potential cure for the majority of patients. 35 , 36 After effective therapy with DLI, CHR and CCyR were detected. Then, the patient received therapy with dasatinib (100 mg daily).…”