title: Lymphodepletion followed by donor lymphocyte infusion (DLI) causes significantly more acute graft-versus-host disease than DLI alone.
abstract: Donor lymphocyte infusions (DLIs) can produce lasting remissions in patients with relapsed chronic myeloid leukemia (CML), but are less effective in non-CML diseases. We hypothesized that lymphodepletion, achieved with cyclophosphamide (Cy) and fludarabine (Flu), would promote in vivo expansion of the infused lymphocytes enhancing their immunologic effects. Fifteen patients with relapsed non-CML disease who received Cy/Flu/DLI were compared with 63 controls who received DLI without chemotherapy. Only the patients receiving Cy/Flu/DLI became lymphopenic at the time of DLI. Compared with controls, patients who received Cy/Flu/DLI developed significantly more grades II to IV (60% vs 24%, P = .01) and grades III to IV acute graft-versus-host disease (GVHD) (47% vs 14%, P = .01) with greater GVHD lethality. In Cy/Flu/DLI patients, T-cell proliferation was elevated at 14 days after DLI. Although these data suggest that chemotherapy-induced lymphodepletion enhances activation of donor lymphocytes, the toxicity needs to be managed before testing whether better disease control can be achieved. This trial was registered at www.clinicaltrials.gov as no. NCT00303693 and www.cancer.gov/clinicaltrials as no. NCT00167180.
authors.affiliation: Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Cancer Center, Minneapolis, MN 55455, USA. mille011@umn.edu
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Burns
authors.forename: Arne
authors.initials: A
authors.lastname: Slungaard
authors.forename: John E
authors.initials: JE
authors.lastname: Wagner
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
authors.forename: Sarah
authors.initials: S
authors.lastname: Cooley
authors.forename: Rosanna
authors.initials: R
authors.lastname: Wangen
authors.forename: Susan K
authors.initials: SK
authors.lastname: Fautsch
authors.forename: Roby
authors.initials: R
authors.lastname: Nicklow
authors.forename: Todd
authors.initials: T
authors.lastname: Defor
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001782:Blood Donors; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D006801:Humans; D017710:Lymphocyte Transfusion / Q000009:adverse effects; D008214:Lymphocytes / Q000166:cytology; D008875:Middle Aged; D019172:Transplantation Conditioning