G-CSF-mobilized donor leukocyte infusions as immunotherapy in acute leukemia relapsing after allogeneic marrow transplantation.

Abstract

Eight patients who relapsed with acute leukemia within a year after allogeneic BMT were treated with G-CSF-mobilized donor leukocyte infusions (mDLI) to induce GvHD as a form of immunotherapy. Prior to mDLI, 7 who had systemic relapse received one (2 AML, 1 ALL, 1 CML myeloid blast crisis) or two (2 AML, 1 ALL) rounds of conventional dose induction chemotherapy, and 1 patient with isolated central nervous system (CNS) lymphoid blast crisis CML received intrathecal chemotherapy followed by craniospinal irradiation. G-CSF (10 microg/kg/day) was given to original HLA-matched sibling donors for 4-5 days before leukapheresis of at least 6.0 x 10(8) mononuclear cells per kilogram of recipient weight. No GvHD prophylaxis was used when mDLI was given in 6 patients at the nadir of hematologic counts and in 2 who were in hematologic remission. There was no regimen-related mortality, as pancytopenic patients had rapid recovery of neutrophil counts (6-18 days after mDLI). All patients developed moderate to severe GvHD (5 grade III/IV, 3 grade II) at a median of 30 days (range 22-59) after mDLI. Two patients died of complications from refractory GvHD while in remission. The other 6 had short remissions lasting 2.2-9.4 months until leukemic relapse as their GvHD was reversed by corticosteroids with or without cyclosporine. Patients who relapse with acute leukemia within a year after BMT still have a poor prognosis. The success of GvHD as a form of immunotherapy in these patients may depend on the ability to control it to a state that is both safe and continually exerting an antileukemia effect.