High Alloreactivity of Low-Dose Prophylactic Donor Lymphocyte Infusion in Patients with Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation with an Alemtuzumab-Containing Conditioning Regimen

Abstract

The value of prophylactic donor lymphocyte infusion (pDLI) is unclear and differs among diseases and transplantation protocols. Experience with this approach in patients with acute leukemia undergoing hematopoietic cell transplantation (HCT) with an alemtuzumab-incorporating conditioning protocol is lacking. We conducted a single-center prospective study to investigate the applicability and efficacy of prophylactic donor lymphocyte infusion (pDLI) in patients with leukemia undergoing HCT with a low-dose alemtuzumab-containing conditioning regimen. Inclusion criteria were high-risk acute myelogenous leukemia, acute lymphoblastic leukemia, or increasing mixed chimerism. All patients included were tapered off of immunotherapy. Exclusion criteria were a history of ≥ grade II or active graft-versus-host disease (GVHD). Of the 56 consecutive patients who underwent HCT with an alemtuzumab-containing regimen, 15 patients (8 with acute myelogenous leukemia and 7 with acute lymphoblastic leukemia) met the study inclusion criteria and received prophylactic DLI (total of 45 infusions) from 7 sibling donors and 8 unrelated donors. The first infusion was given at a median of 162 days posttransplantation. The median number of DLIs was 3, and the median cumulative CD3(+) cell dose was 2 × 10(6)cells/kg. Six of the 8 patients (75%) who received pDLI while in mixed chimerism converted to stable, complete donor chimerism. Some 47% of DLI recipients developed GVHD (4 acute GVHD and 3 with chronic GVHD) after a median cumulative dose of 2 × 10(6) CD3(+) cells/kg. After a median follow-up of 575 days, 11 (73%) pDLI recipients were alive. All 4 deaths were due to GVHD-related causes. None of the patients who received pDLIs relapsed. Patients with leukemia who received low-dose pDLI after conditioning with alemtuzumab are at low risk for relapse; however, this approach is associated with a relatively high incidence of severe GVHD.

Long-term results of adjuvant donor lymphocyte transfusion in AML after allogeneic stem cell transplantation

“…14,15 Our data represent, by far, the largest study on the use of aDLT in high-risk AML after RIC with long-term follow-up and incorporate a well-matched control group. Abbreviation: aDLT = adjuvant transfusion of donor lymphocyte.…”

“…10,14,17,18 Alternatively, to the truly adjuvant application, DLT may also be administered in a preemptive setting guided by mixed chimerism or the detection of minimal residual disease. 10,15,19,20 In our study, five patients are included who have been treated with DLT in a preemptive setting. One patient with low chimerism at day +30 reached full donor chimerism after early DLT infusion, whereas four patients with declining donor chimerism could not be rescued and relapsed despite of DLT.…”

“…Hence, our limited experience with high-risk AML patients differs from studies showing better success in chimerism-guided preemptive DLT therapy. 10,15,21,22 Interventions based on minimal residual disease detection are promising. Yan et al 23 recently published a study on a large cohort of standard-risk AML patients showing improved outcome of minimal residual disease-positive patients after treatment with modified donor lymphocytes.…”

Prophylactic donor lymphocyte infusion in patients with high-risk acute myeloid leukemia: ready for prime time?

“…Another prospective study of prophylactic DLI in patients with high-risk acute leukemia has been reported by Liga et al 19 2 years ago. In that study, patients were given allo-HCT following a low-dose (10-20 mg total dose) alemtuzumab-containing conditioning regimen.…”

“…These approaches include decreasing the level of post-grafting immunosuppression, 13 preemptive (i.e., administered in patients with post-transplant evidence of minimal residual disease or low / decreasing donor chimerism levels) or prophylactic administration of diseasespecific medications such as demethylating agents 14 or FLT3 inhibitors, 15 or preemptive 16,17 or prophylactic DLI. 18,19 In this issue of Bone Marrow Transplantation, Jedlickova et al 20 report the results of a retrospective analysis assessing the safety and efficacy of prophylactic DLI in a cohort of 46 high-risk AML patients given grafts following a sequential treatment consisting of chemotherapy (FLAMSA) followed by RIC allo-HCT. Post-grafting immunosuppression included cyclosporine tapered from day +60 to +90 and mycophenolate mofetil discontinued by day +45.…”