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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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Submitted May 14, 2007
Accepted June 14, 2007
Lymphodepletion followed by donor lymphocyte infusion (DLI) causes significantly more acute graft-versus-host disease than DLI alone
Jeffrey S. Miller*, Daniel J Weisdorf, Linda J Burns, Arne Slungaard, John E Wagner, Michael R Verneris, Sarah Cooley, Rosanna Wangen, Susan K Fautsch, Roby Nicklow, Todd DeFor, and Bruce R Blazar
Div of Hematology, Oncology & Transplantation, Dept of Medicine, Blood & Marrow Transplant Prog & Cancer Center, Univ of Minnesota Cancer Center, Minneapolis, MN
Div of Pediatric Hematology, Oncology & Transplantation, Dept of Pediatrics, Blood & Marrow Transplant Prog & Cancer Center, Univ of Minnesota Cancer Center, Minneapolis, MN
Blood & Marrow Transplant Prog & Cancer Center, Univ of Minnesota Cancer Center, Minneapolis, MN
* Corresponding author; email: mille011{at}umn.edu.
Donor lymphocyte infusions (DLI) 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 to 63 controls who received DLI without chemotherapy. Only the patients receiving Cy/Flu/DLI became lymphopenic at the time of DLI. Compared to controls, patients who received Cy/Flu/DLI developed significantly more grade II-IV (60% vs. 24%, P=0.01) and grade III-IV acute graft-versus-host disease (GVHD) (47% vs. 14%, P= 0.01) with greater GVHD lethality. In Cy/Flu/DLI patients, T-cell proliferation was elevated by 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 #NCT00303693 and www.cancer.gov/clinicaltrials as #NCT00167180.
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