Imatinib Combined with Allogeneic Stem Cell Transplantation for Chronic Myeloid Leukemia.
Authors: Luo Yi , Huang He , Tan Yamin , Han Xiaoyan , Zhu Xiaoli , Lai Xiaoyu , Zhen Cai , Lin Maofang 
Published: October 2019

Abstract
Imatinib has been introduced as the most effective drug for patients with chronic myeloid leukemia (CML) in chronic and advanced phases, but allogeneic stem cell transplantation (Allo-SCT) is still regarded as the only curative treatment option. The main obstacles to successful Allo-SCT for CML in advanced phase are increased post-transplant relapse and high treatment-related mortality. Individual transplantation protocol for CML in chronic and advanced phases should be studied in the imatinib era. To evaluate the exact role of imatinib combined with Allo-SCT for CML, 35 cases of CML between May 2004 and April 2007, with 27 in chronic phases, 4 in accelerated phase and 4 in blast-crisis phase, were studied in our center. 35 patients, 26 males and 10 females with a median age of 35 years (18∼50 years), received the imatinib therapy (400∼600 mg/d) for a median of 3 months (2∼6 months) before transplantation. All of the patients achieved complete hematological remission pre-transplant. Donors were siblings (n=20) or unrelated donors (n=15), and the stem cells were collected from either mobilized peripheral blood (n=24) or bone marrow (n=11). 22 patients with CML in early chronic phases received the nonmyeloablative regimen, including fludarabine 30 mg/m2/day (days −10 to −5), oral busulfan 4 mg/kg/day, or intravenous busulfan 3.2 mg/kg/day (days −6 to −5) and ATG 5mg/kg/day (days −4 to −1). In addition, other 5 patients in chronic phases beyond one year from diagnosis, 4 patients in accelerated phase and 4 in blast-crisis phase received the myeloablative regimen with oral busulfan 4 mg/kg/day, or intravenous busulfan 3.2 mg/kg/day (days −7 to −4) plus cyclophosphamide 60mg/kg/d (days −3 to −2). Mycophenolate mofetil combined with cyclosporin A and methotrexate was used to prevent aGVHD. Engraftment of neutrophils and platelets was achieved in 33 out of 35 (93.3%) patients within a median of 12 days (8∼26 days) and 15 days (0∼35 days), respectively. In myeloablative group, all patients achieved completed engraftment. In nonmyeloablative group, graft failure occurred in two patients, and mixed chimerism occurred in 4 patients while two achieved complete chimerism by the treatment of imatinib and the other two patients by imatinib combined with donor lymphocyte infusion. aGVHD was observed in 8 patients (22.86%) while no patients developed III-IV aGVHD, and cGVHD was observed in 12 patients (37.50%). With a median follow-up of 9.5 months (2.0∼37.0 months), 2 patients relapsed and 3 patients died following transplantation. OS and DFS rates were 91.43% and 82.86%, respectively. In nonmyeloablative group, just one patient relapsed at one year post-transplantation; two patients died from transplanted related complication, one of whom died from interstitial pneumonia at 2 months post-transplantation, and the other occurred cGVHD with bronchiolitis obliterans died at 11 months post-transplantation. In myeloablative group, one in blast-crisis phase before imatinib treatment pretransplant died at 4 months post-transplantation, and the other 12 patients achieved complete molecular remission. Conclusion: Nonmyeloablative Allo-SCT combined with imatinib for CML, with the associated reduction in transplant related mortality and strong GVL effect, is an effective and safe treatment choice for patients in early chronic phase. CML in advanced phase had an excellent outcome after myeloablative Allo-SCT when performed in the phase of cytogenetic response to imatinib.