Clofarabine-based reduced intensity conditioning regimen with peripheral blood stem cell graft and post-transplant cyclophosphamide in adults with myeloid malignancies

Abstract

BackgroundThe Baltimore reduced-intensity conditioning (RIC) regimen using high-dose post-transplant cyclophosphamide (PTCY) is considered as a standard of care for haploidentical allogeneic stem cell transplantation (allo-SCT). However, it is associated with relatively low survivals and high incidence of relapse, especially when considering myeloid malignancies.ResultsThis retrospective study included 36 adults (males n = 18; median age: 60.5 years old; haplodonors n = 27; matched donors n = 8) with myeloid malignancies transplanted between March 2014 and March 2017 at the University Hospital of Nantes. Very encouraging results were observed with a 18-month overall survival (OS), disease-free survival (DFS) and relapse incidence (RI) of 72% ± 7.5%, 63.8 ± 8%, and 25 ± 6% respectively, and a GVHD relapse-free survival (GRFS) of 52.6 ± 8%. In univariate analysis, there were no differences regarding 18-month survivals between patients allografted: i) for acute myeloid leukemia vs myelodysplastic syndrome (OS 70 ± 11% vs 69.2 ± 13%, p = 0.3; DFS 64.7 ± 11% vs 61.5 ± 13%, p = 0.65), or ii) with haplo-identical vs other donors (OS: 66.2 ± 9% vs 88.8 ± 10.4%, p = 0.16; DFS 59 ± 9.5% vs 77.8%, p = 0.6).ConclusionThe “Clo-Baltimore regimen” is safe and feasible and provides good survivals for patients with myeloid malignancies and haplo-donors.MethodsHere, we report a variant of the Baltimore regimen, where 1) fludarabine was replaced by clofarabine, 2) bone marrow was replaced by peripheral blood stem cells, and 3) tacrolimus was replaced by cyclosporine, in a “Clo-Baltimore regimen”.

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

“…We have also recently reported our experience of a “Clo-Baltimore” RIC regimen for myeloid malignancies where fludarabine is replaced by clofarabine as part of a standard Baltimore regimen. The results of this approach in 36 patients showed 18-month OS and DFS of 72% + 7.5%, and 63.8 + 8%, respectively, and a GRFS of 52.6 + 8% [37].…”

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

“…Other studies [26,29] have also observed a high incidence of TRM after haplo-Allo-SCT with TBF conditioning, including one showing, as for us, no influence of the intensity of the conditioning regimen [29]. Thus, other regimens with low TRM may be preferred when considering PBSC haplo-Allo-SCT with PTCY, such as a reinforced Baltimorebased regimen with clofarabine (11% of NRM) [13] or treosulfan-based regimen (17% of NRM) [30].…”

“…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.…”

Phase I/II multisite trial of optimally dosed clofarabine and low‐dose TBI for hematopoietic cell transplantation in acute myeloid leukemia

“…Trials combining clofarabine with high‐dose TBI have been restricted to children and young adults . Because of its immunosuppressive effects, clofarabine has also been studied in haploidentical pediatric HCT and in adult haplotransplant, using a modified Baltimore regimen with 2 Gy TBI and post‐transplant cyclophosphamide …”