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Fludarabine, Cyclophosphamide And Antithymocyte Globulin (ATG) As Conditioning Regimen In Matched Related And Unrelated Allogeneic Stem Cell Transplantation For Severe Aplastic Anemia (SAA): The M.D. Anderson Cancer Center Ten-Year Experience

Year: 2010

Type: article

Abstract: Total body irradiation (TBI) is often employed in matched unrelated donor (MUD) allogeneic stem cell transplantation (allo-SCT) in SAA. However, even at low doses, TBI can cause serious short- and long-term toxicities. In matched related donors (MRD), outcome in SAA patients≥40 years with high-dose cyclophosphamide (CY)±ATG is poor due to graft rejection, GVHD and organ failure. Aim: To explore feasibility of a fludarabine (FLU)–based, high-dose ATG, TBI-free regimen in MUD (all ages) and MRD (recipient>40 years) allo-SCT. Over a 10-year period (1999-2009), twenty SAA patients underwent allo-SCT with a FLU-CY-ATG regimen from a MRD (n=7, all age≥40) or a MUD (n=13, any age). Median age was 34 years (range 1-59). Seven pts (33%) were≥50 years old. Bone marrow was used as SC source in all but four patients. Once the regimen was standardized, it included (n=13) FLU (30 mg/m sq × 4 days) intravenously (IV), CY (300 mg/m sq IV × 4 days), and thymoglobulin (THY, 3.75 mg/kg IV × 3-4 days). Before that, in seven patients doses were FLU 20-50 mg/m sq IV × 4 days; CY 40-60 mg/kg IV × 2-4 days; ATG IV 20-30 mg/kg (horse product) or 3 mg/kg (THY) x 2-4 days. Median time from diagnosis to allo-SCT was 12 months (2-244). Eleven patients (55%) were transplanted off study (active infection, poor organ function, etc). Seventeen out of 19 evaluable patients engrafted (90%). There were two secondary graft failures (10%). Median time to neutrophil recovery (i.e. absolute neutrophil count≥500/mL) was 15 days (range 8-30). Chimerism studies indicated ≥90% donor-derived engraftment in 16/19 evaluable patients (75%) and thirteen patients were 100% donor. Four out of 20 evaluable patients (20%) developed acute grade II-IV GVHD, and 6/16 evaluable patients (37%) developed chronic GVHD. Thirteen patients (62%) are alive (including eight out of the last nine treated) with a median follow-up of 30 months (3-112). Seven patients expired (graft rejection n=1, infection n=2, GVHD n=1, organ failure n=1, EBV lymphoproliferative disorder/LPD n=2). There was one early death (death < day +30) and no known late graft failures. Fludarabine-based, TBI-free for MRD and MUD allo-SCT is feasible in this high-risk group (older age, active infection, poor organ function, etc), with high engraftment rates and low early mortality. Presumably due to high-dose ATG, GVHD-related incidence and mortality were low, although EBV LPD was a drawback.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2009.12.194