Donor lymphocyte infusion followed by interferon-alpha plus low dose cyclosporine A for modulation of donor CD3 cells activity with monitoring of minimal residual disease and cellular chimerism in a patient with first hematologic relapse of chronic myelogenous leukemia after allogeneic bone marrow transplantation

A 15-year-old girl with Ph-positive chronic myelogenous leukemia in first c hronic phase received bone marrow from her human leukocyte antigen matched brother. Twenty three months after bone marrow transplantation hematologica l relapse occured which was treated with two infusions of donor lymphocytes (DLI) (0.5 x 10(8) CD3/kg b.w./infusion). To enforce the graft-versus-leuk emia effect (GvL), the first DLI was followed by administration of interfer on-alpha (INF-alpha) 6 x 10(6) U/day for 30 days, whereas, after the second infusion INF-alpha was given at the same dose until hematological remissio n was achieved (80 doses). Minimal residual disease (MRD) was detected by c onventional cytogenetics (Ph chromosome), fluorescence in situ hybridizatio n (FISH) cytogenetics (BCR/ABL translocation) and reverse transcriptase-pol ymerase chain reaction (RT-PCR) Ecotropic virus integration site-1 (EVI-1 g ene expression), whereas cellular chimerism was monitored by assessment of microsatellite markers PCR and Y-chromosomal DNA content FISH. When hematol ogical remission was achieved the pancytopenia was observed and the cytogen etic and molecular investigations revealed only partial remission and mixed chimerism, however, with predominance of donor origin hematopoiesis. To di minish the myelosupressive effect of donor CD3 cells without switching-off the GvL effect, a low dose of cyclosporine A was given. Further observation revealed significant improvement of hematopoiesis with parallel gradual de cline of MRD and increase of donor hematopoiesis up to complete chimerism. Graft-versus-host disease was not observed at any stage of the treatment. ( C) 2001 Elsevier Science Ltd. All rights reserved.