Fludarabine, Low Dose Busulfan and Antithymocyte Globulin (ATG) Compared to Fludarabine and Low Dose Total Body Irradiation (TBI) for Reduced-Intensity Conditioning (RIC) Prior to Allogeneic Stem Cell Transplantation (allo-SCT) In Patients with Lymphoid Malignancies.
Authors: Malard Florent , Brissot Eolia , Chevallier Patrice , Guillaume Thierry , Delaunay Jacques , Ayari Sameh , Mahe Beatrice , Dubruille Viviane , Gastinne Thomas , Blin Nicolas , Saulquin Beatrice , Harousseau jean Luc , Moreau Philippe , Milpied Noel , Gouill Steven Le , Mohty Mohamad 
Published: October 2019

Abstract
Abstract 3472
Allo-SCT procedures are currently undergoing a profound evolution. The spectra of patients and diseases for which this approach is now considered have increased considerably over the past years. This is mainly due to the introduction in routine practice of the so-called nonmyeloablative or RIC regimens. While it is well established that fludarabine is the backbone drug to secure engraftment, there is a wide variability in the degree of myeloablation between the different RIC protocols, and the toxicity profile might vary significantly from one protocol to another. The combination of fludarabine and Busulfan (usually 8 mg/Kg total dose) with or without ATG, is among the most widely used RIC protocols worldwide.
In an attempt to further decrease the toxicity of the transplant procedure, we hypothesized that further reduction (50%) of the Busulfan dose can allow improving transplant outcome for lymphoid neoplasms. With this background, this retrospective analysis was performed to assess whether a RIC regimen including fludarabine (120 mg/m2), low dose busulfan (4 mg/Kg total dose administered orally over a single day) and ATG (Thymoglobuline®, 2.5 mg/Kg/d for 2 days; FB1A protocol, n=44), is a valid alternative to the classical RIC regimen including fludarabine (90 mg/m2) and TBI (2 Gy.) (FTBI, n=27) prior to allo-SCT.
The cohort included 37 males (52%) and 34 females (48%) treated consecutively in a single centre, with a median age at time of allo-SCT of 53 (range, 15–66) y. Diagnoses included 39 NHL (55%), 17 Hodgkin lymphomas (24%), 12 CLL (17%) and 3 myeloma (4%). PBSCs were used as stem cell source in 42 patients (91%), while 4 patients (9%) received classical bone marrow. A matched-related donor was used in 18 cases (39%) and an unrelated donor in 28 cases (61%). With a median follow-up of 43 (range, 3.7–85) months after allo-SCT, all patients, but one (from the FTBI group) engrafted. In the FB1A group, the acute grade 3–4 GVHD rate was 20.5% (n=9), the chronic GVHD rate was 32% (n=14), the relapse rate was 23% (n=10) and the TRM rate was 25% (n=11). In the FTBI group, the rate of grade 3–4 acute GVHD rate was 44% (n=12; P=0.03 in comparison to the FB1A group), the chronic GVHD rate was 52% (n=14; P=0.09), the relapse rate was 15% (n=4; P=NS) and the TRM rate was 37.0% (n=10; P=NS). At 2 years, overall survival was 66% (95%CI, 51–78%) in the FB1A group versus 55% (95%CI, 36–73%) in the FTBI group (P=NS). Disease-free survival (DFS) was also comparable between both groups (at 2 years, 59% in the FB1A group, vs. 48% in the FTBI group, P=NS). In a Cox multivariate analysis for OS or DFS, the type of RIC regimen was not significantly associated with outcome.
In all, these results suggest that in patients with lymphoid malignancies, a RIC regimen including Fludarabine, ATG and low dose busulfan (4 mg/Kg total dose) is a valid alternative to the classical Fludarabine and low dose TBI-based RIC regimen with a favorable toxicity profile and efficient disease control.

Disclosures:
No relevant conflicts of interest to declare.