Journal
BLOOD
Volume 110, Issue 7, Pages 2761-2763Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-05-090340
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Funding
- NCI NIH HHS [R01 CA072669, P01 CA65493, R01 CA72669, P01 CA111412, P01 CA065493] Funding Source: Medline
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Donor lymphocyte infusions (DLIs) can produce lasting remissions in patients with relapsed chronic myelold 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/FIu/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/FIu/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.
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