Comparison of Reduced-Intensity Conditioning Regimen and Conventional Conditioning Regimen for Allografting in Chronic Myeloid Leukemia in the First Chronic Phase.
Authors: Doubek Michael , Krejci Marta , Brychtova Yvona , Mayer Jiri 
Published: April 2020

Abstract
The role of conventional allogeneic blood stem cells transplantation (SCT) in the treatment of chronic myeloid leukemia (CML) in the first chronic phase (CP) is not exactly defined yet. The role of allogeneic transplantation after the reduced-intensity conditioning regimen is even more unclear. Our work aims to compare the effect of reduced-intensity conditioning regimen and conventional conditioning regimen in the treatment of CML in the first CP. We performed a retrospective analysis of the patients with CML, who underwent the allogeneic SCT in our department from 1997 after a conventional regimen BuCy (busulfan in a total dose of 14–16mg/kg and cyclophosphamide in a total dose of 120 mg/kg) and after reduced-intensity regimen comprising of fludarabine (Flu, in a dose 30 mg/m2/d, 6 days) oral busulfan (Bu) in a total dose 8 mg/kg, and ATG at a dose of 10 mg/kg/d (4 days). For the analysis we chose as comparable groups of patients as possible. We analysed only patients with transplanted peripheral blood stem cells from their HLA identical sibling. Into the analysis we included 17 patients transplanted after the regimen BuCy and 13 patients transplanted after the regimen Flu+Bu+ATG. The patients transplanted after the regimen Flu+Bu+ATG were significantly older in comparison to the patient transplanted after the regimen BuCy (median of 51 years compared to 33 years). The median period from the date of diagnosis till the date of transplantation was 6 months in regimen Flu+Bu+ATG and 5 months in regimen BuCy. A profylaxis of the graft-versus-host disease (GVHD) comprised of cyclosporine A in regimen Flu+Bu+ATG and of cyclosporine A plus methotrexate in regimen BuCy. After the regimen BuCy we noticed higher mortality till the day +100 (11.8% versus 0; p&lt;0.01), higher incidence of acute GVHD (76.5% versus 38.5%; p=0.05), higher incidence of hepatic veno-occlusive disease (VOD) (11.8% versus 0; p&lt;0.01) and higher non-hematologic toxicity (100% versus 76.5%; p&lt;0.01). The two compared regimens do not significantly differ in the incidence of chronic GVHD, cytomegalovirus reactivation and febrile neutropenia. We did not find any difference in the induction of complete chimerism after the transplantation. After the regimen BuCy it was observed that the achievement of complete molecular remission (CMR) of the disease was faster. Six months after transplantation, the ratio of patients in CMR was 64.7% (BuCy) versus 46.1% (Flu+Bu+ATG). At the present time 70.6% of patients transplanted after the regimen BuCy and 76.9% after the regimen Flu+Bu+ATG are in CMR. Stable sustained CMR has been observed in 70.6% of patients treated by regimen BuCy and in 53.8% of patients treated by Flu+Bu+ATB (non-significant). Four patients died consequent to the transplantation after the regimen BuCy (on VOD, bleeding, ARDS and extensive chronic GVHD with sepsis) and one patient after the regimen Flu+Bu+ATG (on relaps of the leukemia and GVHD after the donor lymphocyte infusion). A long-term survival is 76.5% of patients transplanted after BuCy and 92.3% of patients transplanted after Flu+Bu+ATG. After the regimen Flu+Bu+ATG we have found 4 relapses (one haematological and 3 molecular), after the regimen BuCy we have found 3 relapses, all of them were molecular. Our comparison shows, that the regimen BuCy is more toxic, on the other hand it leads to sustained CMR more often. When analysing the overall survival, both regimens are equal, despite the fact that the regimen Flu+Bu+ATG was used in older patients.