Response and toxicity of donor lymphocyte infusions following T-cell depleted non-myeloablative allogeneic hematopoietic SCT from 3-6/6 HLA matched donors.
We report the outcome of early donor lymphocyte infusions (DLIs) after T-cell depleted non-myeloablative transplantation using stem cells from HLA-matched or mismatched donors. Sixty-nine patients with high-risk hematologic malignancies received DLI following fludarabine, CY and alemtuzumab with infusion of stem cells from a matched sibling (52) or partially matched family member donor (17). Patients received the first infusion at a median of 50 days after transplant, and doses ranged from 1 x 10(4) CD3+ cells/kg to 3.27 x 10(8) CD3+ cells/kg, depending on clinical status and the physician's discretion. A median cell dose of 1 x 10(5) CD3+ cells/kg in the mismatched setting and 1 x 10(6) CD3+ cells/kg in the matched sibling setting appears safe with only 1 of 7 (14%) and 4 of 31 patients (13%), respectively, experiencing severe acute GVHD at these doses. Importantly, 38% of patients with persistent disease before DLI attained a remission after infusion. Nine of the 69 patients remain alive and disease-free 32-71 months after the first DLI. In conclusion, low doses of DLI can be safely provided soon after T-cell depleted non-myeloablative therapy and provide a chance of remission. However, long-term survival still remains poor, primarily because of relapse in these patients.
Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. rizzi003@mc.duke.edu
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Rizzieri
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Dev
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Long
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Gasparetto
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Sullivan
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Horwitz
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Chute
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Chao
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D006085:Graft Survival / Q000276:immunology; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D017710:Lymphocyte Transfusion / Q000009:adverse effects / Q000379:methods*; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D011446:Prospective Studies; D017741:Survivors; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
D006680:HLA Antigens; D019653:Myeloablative Agonists