Induction of a graft-versus-leukemia reaction by cyclosporin A withdrawal as immunotherapy for leukemia relapsing after allogeneic bone marrow transplantation

We studied the immunomodulating effect of withdrawal of immunosuppression w ith cyclosporin A (CsA) in 42 patients with leukemic relapse of chronic mye logenous leukemia (CML) (n = 24), acute myeloid leukemia (AML) (n = 13) and acute lymphoblastic leukemia (ALL) (n = 5) after allogeneic unmanipulated bone marrow (BMT) or peripheral blood stem cell transplantation (PBSCT), Re sponse to CsA withdrawal was monitored molecularly by the polymerase chain reaction for elimination of CML cells containing the bcr-abl messenger RNA (mRNA) transcript (n = 24), or mll-af4 mRNA transcript characteristic of le ukemic cells with a 11q23 chromosomal abnormality (n = 1), Rapid tapering o f CsA resulted in subsequent achievement of cytogenetic remission in 11 of 14 CML patients (79%) who relapsed in early disease phase (n = 9 cytogeneti c relapse, it 2 hematological relapse) after a median of 57 days. Three of 13 AML patients and one of five ALL patients achieved complete remission. C sA withdrawal was accompanied by the development of acute graft-versus-host disease (GVHD) grade II in most of the 24 patients with CML. Two patients who achieved remission of AML or ALL died from severe GVHD grade III-IV, We calculated a probability of 84% for achieving and remaining in remission w ith early relapse of CML 4 years after relapse post BMT, whereas patients w ith AML have only a probability of about 10% of achieving and remaining in remission after 3 years. Patients with advanced CML and ALL had no chance o f achieving and remaining in remission in the same time period.