No-Myeloablative Conditioning Regimen Cyclosphophamide-Fludarabine-ATG (Cy-Flu-ATG) Results in Better Overall Survival Compared with Myeloablative Doses of Cy with or without ATG, in High-Risk Bone Marrow Failure Syndromes (BMFS) Patients

Allo-SCT from an HLA related or unrelated donor is the first line treatment for newly diagnosed patients with BMFS younger than 40 years, and for older patients that failed immunosuppressive therapy.

Cohort retrospective analysis of BMFS patients receiving Allo-SCT in a mixed (pediatric-adult) transplant center in Bogota, Colombia, was performed to assess the influence of different conditioning regimens in outcomes. Log-rank tests (Lrt) analyses were used to determine the effects of age, conditioning regimen and year of treatment on survival.

Between January 1995 and August 2013, 96 transplants were performed in 89 patients (70 acquired SAA, 16 Fanconi Anemia, 2 pure red cell aplasia, 1 dyskeratosis congenita). 54 were males, mean age 25.8 years (range 4-60), mean time from diagnosis to transplant 26.2 months (range 2.1-143), 60% were heavily transfused. Most donors were HLA identical siblings (81 PBSC, 7 BM); 3 transplants from unrelated CBU, 2 from an haploidentical relative and 2 from an HLA identical URD. Conditioning regimens used were: RIC Cy-Flu-ATG (41), Cy-ATG (35) and Cy (14). 6 patients were conditioned with Campath containing regimens and 2 with other. Before 2004 most patients received Cs and MTX as GVHD prophylaxis, after 2004 Cs and MMF was used in the majority.

2 patients died due to sepsis before engraftment could be evaluated. From the 87 evaluable patients, 5 had primary graft failure and 4 secondary graft failure. 7/9 patients with graft failure had a second transplant (5 from the same donor and 2 from an haploidentical relative). 6 of those 7 transplants engrafted and are alive. Non-myeloablative conditioning containing Fludarabine, resulted in less hospital stay compared to Cy-ATG and Cy alone (22.9, 32, 33 days respectively), less fever (1.7, 6.7, 7 days), less parenteral nutrition (0.1, 9, 4 days) and less red cells (2.4, 3.8, 3.8) and platelet (4.5, 7.5, 9.75) transfusions. Rates of GII-IV aGVHD were also less frequent for Cy-Flu-ATG group 8% compared to Gy-ATG (18%) or Cy (25%). Extensive cGVHD was reported in 11%, 6% and 25% respectively.

The median follow-up was 23.06 months (range: 7.06-62.6). Five-year overall survival (OS) was 69.23% for the entire group. RIC-Flu-Cy-ATG resulted in significantly better overall survival (85.7%) compared to other regimens (66.6% for Cy-ATG and 28.5% Cy (p=0.0016). There was no significant difference in survival related to age (p=0.96). There as superior survival for transplants performed after 2004 (n=64) compared with those before that year (n=25) (80.3 vs 43.3%, p=0.004).

This single center experience suggest significant overall survival advantage of RIC-Flu-Cy-ATG over other conditioning regimens in high-risk BMFS patients regardless the age. These results should be validated in prospective randomized studies.