Long-Term Follow up of SAA Patients Allografted with a Non-ATG-Based Conditioning Regimen, Using Pbscs As the Sole Source of Engraftment: A Single Center Experience of 53 Patients Above the Age of 20 Years

Long-term follow up of SAA patients allografted with a non-ATG-based conditioning regimen, using PBSCs as the sole source of engraftment: A single center experience of 53 patients above the age of 20 years.

Omar A Fahmy^1&2, Hosam K Mahmoud^1&3, Alaa El-Haddad^1&3, Gamal Fathy¹ and Noha El-Hussainy².

1. BMT unit, Nasser Institute, Cairo; 2. Demartment of Medicine, Clinical Hematology Unit, Cairo University; 3. National Cancer Institute, Cairo University, Egypt.

 

Background:  Allogeneic HSCT from an HLA-matched sibling donor is the recommended treatment approach in patients with SAA, at least up to the age of 40 years. Cyclophosphamide (Cy)-ATG is the standard, non-myeloablative conditioning regimen, while BM stem cells are the preferred source of engraftment.

Aims:  We have already published our data regarding the use of PBSCs in patients with SAA conditioned with the Fludarabine (Flu)-Cy regimen (EBMT, Czech Republic 2005, Poster Abst # 782 / CBMTG, Montreal 2008, oral Abst # 02). In this single arm prospective study, we investigated the use of Flu–Cy  to allograft SAA patients >20 years old, using PBSCs.  

Patients & methods:  In the time period between May 2003 and December 2009, 53 heavily pre-transfused SAA patients  received allogeneic HLA- identical sibling PBSCs  at the BMT unit of Nasser institute, Cairo, Egypt. All patients were above the age of 20 years (range 21- 41 years, mean 27 years). The regimen consisted of  Flu at a total dose ranging from 75mg-120mg/ m2, and a total Cy dose of 200mg/kg. Our primary endpoints were  incidence and severity of  chronic GVHD, as well as DFS & OS. Cyclosporine & Methotrexate were used for GVHD prophylaxis.

Results:   The mean number of infused CD34+ve cells was  6.7x 10⁶  /kg recipient weight.  All patients engrafted rapidly at a median rate of 15 days for neutrophils and 16 days for platelets. Although the total incidence of cGVHD was 43%, only 17% had extensive cGVHD, and the remaining 26% had the limited form which was very well controlled under a small-dose of immuno-suppressive therapy. By sub-group analysis, we found that the vast majority of patients with extensive cGVHD received the initial lower dose of Flu (75mg/m2), and half of them were >30 years old. Since then, we’ve standardized the dose to be 120mg/m2. At a follow up period of up to 9 years (median 5.9 years), both DFS & OS were 79.2%.

Conclusion:  Allografting SAA patients with PBSCs, using the Flu-Cy regimen has a significantly lower cost, with excellent  tolerability, and promising outcome regarding engraftment, DFS & OS. The incidence of cGVHD can be considered acceptable, putting in mind the higher patients’ age and the initial lower dose of Flu that we’ve used. However, this approach definitely needs a larger cohort of patients to be randomly compared to the standard Cy-ATG regimen with the use of BM cells.