Blood, 1 October 2007, Vol. 110, No. 7, pp. 2761-2763.
Prepublished online as a Blood First Edition Paper on June 19, 2007; DOI 10.1182/blood-2007-05-090340.
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TRANSPLANTATION
Brief Report
Lymphodepletion followed by donor lymphocyte infusion (DLI) causes significantly more acute graft-versus-host disease than DLI alone
Jeffrey S. Miller1,
Daniel J. Weisdorf1,
Linda J. Burns1,
Arne Slungaard1,
John E. Wagner2,
Michael R. Verneris2,
Sarah Cooley1,
Rosanna Wangen3,
Susan K. Fautsch3,
Roby Nicklow3,
Todd DeFor3, and
Bruce R. Blazar2
1 Division of Hematology, Oncology and Transplantation, Department of Medicine
2 Division of Pediatric Hematology, Oncology and Transplantation, Department of Pediatrics
3 Blood and Marrow Transplant Program and Cancer Center, University of Minnesota Cancer Center, Minneapolis
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
[ClinicalTrials.gov]
and www.cancer.gov/clinicaltrials as no. NCT00167180
[ClinicalTrials.gov]
.
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