Clofarabine/busulfan-based reduced intensity conditioning regimens provides very good survivals in acute myeloid leukemia patients in complete remission at transplant: a retrospective study on behalf of the SFGM-TC

Abstract

BackgroundClofarabine has been proved to have higher anti-leukemic myeloid activity compared to fludarabine, a drug extensively used as part of reduced intensity conditioning (RIC) for allogeneic stem cell transplantation (allo-SCT).ResultsEighty-four patients were included. The majority of patients had acute myeloid leukemia (AML, n = 63). Sixty-one patients were in complete remission (AML n = 55). With a median follow up of 31 months (range: 5.7–74.1), 2-year overall (OS) and disease-free (DFS) survivals, relapse incidence (RI), non-relapse mortality (NRM) and graft-versus-host disease (GVHD)/relapse free survival (GRFS) were 64.5% (53.8–75.2); 57.2% (46.2–68.2); 27.7% (18.2–37.9); 15.1% (8.2–23.9) and 43.6% (32.5–54.7), respectively. Considering AML in remission, 2-year OS, DFS, RI, NRM and GRFS were 74.2% (62–86.5); 66.8% (53.6–79.9); 23.4% (12.7–36); 9.8% (3.5–19.9) and 50.9% (36.9–64.9), respectively. Two-year outcomes were similar between CloB2A1 and CloB2A2 sub-groups. In multivariate analysis, active disease at transplant was the only factor adversely impacting 2 years outcomes.ConclusionsCloB2A2/A1 RIC regimen provides very good results for AML patients allografted in CR and could be retained as a new RIC platform for these patients.Materials and MethodsThis was a retrospective study including all patients who received a clofarabine/busulfan based RIC allo-SCT for myeloid malignancies and reported within the SFGM-TC registry. RIC regimen consisted of clofarabine 30 mg/m2/day 4 to 5 days (Clo), busulfan 3.2 mg/kg/day 2 days (B2) and 2.5 mg/kg/day of rabbit anti-thymocyte globulin 1 or 2 days (A1 or A2). The primary objective of the study was to report the main outcomes of the whole cohort at 2 years.

Grade 2 acute GVHD is a factor of good prognosis in patients receiving peripheral blood stem cells haplo-transplant with post-transplant cyclophosphamide

“…Surprisingly, CloB2 was associated with a higher rate of graft failure, suggesting that this regimen is not immunosuppressive enough, although ATG was systematically administered with PTCY/ cyclosporine and MMF for these patients. Conversely, CloB2 was confirmed to be very efficient for matched grafts, especially in AML [14]. CloB2 conditioning should thus probably not be prescribed for patients receiving a haplo-identical graft.…”

“…Three conditioning regimens were used: (i) a Baltimore-based RIC regimen with fludarabine [2] or clofarabine [13]; (ii) a CloB2 regimen [14] or (iii) a TBF regimen [15]. The three conditioning regimens were used in Nantes while the Besanc¸on team used TBF only.…”

Influence of Donor Type (Sibling versus Matched Unrelated Donor versus Haploidentical Donor) on Outcomes after Clofarabine-Based Reduced-Intensity Conditioning Allograft for Myeloid Malignancies

“…Patients allografted with MSDs or MUDs received a CloB2A1/A2 RIC regimen consisting of clofarabine 30 mg/m 2 /day for 4 to 5 days (Clo), busulfan 3.2 mg/kg/day for 2 days (B2), and 2.5 mg/kg/day of rabbit antithymocyte globulin for 1 or 2 days (A1 or A2) [4,6]. Patients allografted with a haplo donor received a Clo-Baltimore regimen consisting of clofarabine 30 mg/m 2 / day on days À6 to À2, cyclophosphamide 14.5 mg/kg on day À6, and lowdose total body irradiation 2 Gy on day À1 [3].…”

“…The median CD34 + PBSC dose infused was 7.39 £ 10 6 /kg of recipient (range, 2.49 to 12.9). The outcomes of some patients were reported previously [3,4] but were updated for the present study. Patient characteristics are given in Table 1.…”

“…Recently we reported the encouraging results of a "Clo-Baltimore" RIC regimen for myeloid malignancies where fludarabine was replaced by clofarabine and bone marrow by peripheral blood stem cells (PBSCs) as the source of graft [3]. Previously we also reported very good outcomes using a "CloB2A1/A2" RIC (clofarabine, busulfan, and antithymocyte globulin) regimen for patients with matched sibling (MSD) or matched unrelated (MUD) donors [4].…”