TY - JOUR
T1 - A Phase I/ii study of chemotherapy followed by donor lymphocyte infusion plus interleukin-2 for relapsed acute leukemia after allogeneic hematopoietic cell transplantation
AU - Inamoto, Yoshihiro
AU - Fefer, Alexander
AU - Sandmaier, Brenda M.
AU - Gooley, Theodore A.
AU - Warren, Edus H.
AU - Petersdorf, Stephen H.
AU - Sanders, Jean E.
AU - Storb, Rainer F.
AU - Appelbaum, Frederick R.
AU - Martin, Paul J.
AU - Flowers, Mary E.D.
PY - 2011/9
Y1 - 2011/9
N2 - The efficacy of donor lymphocyte infusion (DLI) for treatment of relapsed acute leukemia after allogeneic hematopoietic cell transplantation is limited. We hypothesized that interleukin-2 (IL-2) combined with DLI after chemotherapy might augment graft-versus-leukemia effects. To identify a safe and effective IL-2 regimen, a phase I/II study of DLI plus IL-2 therapy was performed for such patients. After chemotherapy, 17 patients received DLI (1 × 10 8 CD3/kg for patients with related donors, and 0.1 × 10 8 CD3/kg for those with unrelated donors) and an escalating dose of induction IL-2 (1.0, 2.0, or 3.0 × 10 6 IU/m 2/day representing levels I [n = 7], Ia [n = 9], and II [n = 1]) for 5 days followed by maintenance (1.0 × 10 6 IU/m 2/day) for 10 days as a continuous intravenous infusion. Unacceptable IL-2-related toxicities developed in 1 patient at level I, 2 at level Ia, and 1 at level II. Grades III-IV acute graft-versus-host disease (aGVHD) developed in 5 patients, and extensive chronic GVHD (cGVHD) developed in 8. Eight patients had a complete remission after chemotherapy prior to DLI, and 2 additional patients had a complete remission after DLI plus IL-2 therapy. In conclusion, the maximal tolerated induction dose of IL-2 combined with DLI appears to be 1.0 × 10 6 IU/m 2/day. IL-2 administration after DLI might increase the incidence of cGVHD.
AB - The efficacy of donor lymphocyte infusion (DLI) for treatment of relapsed acute leukemia after allogeneic hematopoietic cell transplantation is limited. We hypothesized that interleukin-2 (IL-2) combined with DLI after chemotherapy might augment graft-versus-leukemia effects. To identify a safe and effective IL-2 regimen, a phase I/II study of DLI plus IL-2 therapy was performed for such patients. After chemotherapy, 17 patients received DLI (1 × 10 8 CD3/kg for patients with related donors, and 0.1 × 10 8 CD3/kg for those with unrelated donors) and an escalating dose of induction IL-2 (1.0, 2.0, or 3.0 × 10 6 IU/m 2/day representing levels I [n = 7], Ia [n = 9], and II [n = 1]) for 5 days followed by maintenance (1.0 × 10 6 IU/m 2/day) for 10 days as a continuous intravenous infusion. Unacceptable IL-2-related toxicities developed in 1 patient at level I, 2 at level Ia, and 1 at level II. Grades III-IV acute graft-versus-host disease (aGVHD) developed in 5 patients, and extensive chronic GVHD (cGVHD) developed in 8. Eight patients had a complete remission after chemotherapy prior to DLI, and 2 additional patients had a complete remission after DLI plus IL-2 therapy. In conclusion, the maximal tolerated induction dose of IL-2 combined with DLI appears to be 1.0 × 10 6 IU/m 2/day. IL-2 administration after DLI might increase the incidence of cGVHD.
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U2 - 10.1016/j.bbmt.2011.01.004
DO - 10.1016/j.bbmt.2011.01.004
M3 - Article
C2 - 21232624
AN - SCOPUS:80051668520
SN - 1083-8791
VL - 17
SP - 1308
EP - 1315
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 9
ER -