Objective: To study the effect of nonmyeloablative allogeneic peripheral blood stem cell (NST) transplantation combined with imatinib in the treatment of chronic myeloid leukemia (CML).
Methods: Ten CML patients, 5 males and 5 females, aged 21-41, 3 in chronic phase (CP), 4 in accelerated phase (AP) and 3 in blast crisis phase (BP), were treated with imatinib (400-1500 mg/d) before (n = 10) and/or after (n = 6) NST transplantation. The donors were HLA-identical (n = 4), 5/6 antigen-matched (n = 2), 4/6 antigen-matched (n = 2), 3/6 antigen-matched (n = 1) siblings or haplo-identical mothers (n = 2). The preparative regimen included cytoxin (CTX), Ara-C, and fludarabine combined with antithymocyte globulin (ATG) or anti-CD3 monoclonal antibody. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (CSA) and mycophenolate mofetil (MMF), or with low-dose methotrexate (MTX) or zenapax.
Results: All the 10 patients showed donor cell chimerism at different degree: three had full chimerism (> 95%) and seven mixed chimerism (44%-95%). Mixed chimerism in 6 cases had been transformed into full chimerism during 1.5-10 months after NST transplantation through immunosuppressive agent withdrawal, donor peripheral blood stem cell/donor lymphocyte infusion or treatment of imatinib. The time needed for increase of the number of neutrophils to more than 0.5 x 10(9)/L was 16 d days (10-21 days). The time needed for increase of the number of platelets more than 20 x 10(9)/L was 10 days (4-15 days). 6 cases had I-II degrees acute and chronic GVHD of skin. 2 case had III-IV degrees chronic GVHD. 2 cases died of transplantation-related complication 27 and 45 days after transplantation respectively. One patient died of III-IV degrees cGVHD. Seven patients remained alive after a median follow-up of 14.5 months (7-23 months). The time needed for bcr/abl becoming negative was 33-130 days. None case relapsed during the following-up.
Conclusion: An effective and safer method for CML, especially advanced CML treatment of NST transplantation combined with imatinib before and after transplantation reduces the leukemic cell load before transplantation, inhibits the proliferation of residual leukemic cells, promotes full chimerism change and enhanced the effect of graft versus leukemia.