Partial T cell depletion for unrelated donor BMT for children with severe aplastic anemia (SAA): engraftment with minimal GVHD

Unrelated donor BMT for SAA is reserved for patients who lack an HLA identical sibling, and fail medical therapy. However, increased graft rejection is a potential problem in these heavily transfused patients (pts), and the risk of severe GVHD is also increased with unrelated donors. Improved techniques in HLA typing to ensure molecular matching may decrease the risk of GVHD, but may limit donor availability. Partial T cell depletion may decrease the risk of severe GVHD, while still maintaining sufficient donor T lymphocytes to ensure engraftment. We report on 12 patients with SAA who underwent unrelated donor BMT. Pts had failed medical therapy with ATG, steroids and cyclosporine (CSA) (9) or relapsed following initial responses (3). Median age was 6 yrs (1–20), and there were 5 males, 7 females. Median time from diagnosis of SAA to BMT was 466 days(155–1084). Donors were serology class I (A, B) and DRB1 matched for 4 pts, mismatched at the A locus for 3 pts, at B locus for 3 pts, and at DR for 2 pts. Conditioning included Ara-C 12 g/m2, cyclophosphamide (CPM) 90 mg/kg and total body irradiation 12–13.2 Gy for 4 pts, and thiotepa 10 mg/kg, CPM 120 mg/kg and TBI 12 Gy for 8 pts. The last 7 pts received ALG 1.5 mg/kg for 3 days prior to marrow infusion. In vitro partial T cell depletion was T10B9 and complement (8 pts) or OKT3 and complement (4 pts). Cyclosporine was used for 3 months post BMT and then tapered. Median nucleated cell dose post T depletion was 0.8 x 108/kg (0.24–3.2), and median CD3+ cell dose was 1 x 106/kg (0.2–9.2). All patients engrafted, with a median time of 18 days to ANC > 500 (14–34), and all but one pt became platelet transfusion independent. Acute GVHD grades I-II developed in 4 pts; two developed limited cGVHD. Nine pts (75%) are alive 3–147 mos post BMT and transfusion independent. Morbidity included intractable VOD in a pt with Schwachman-Diamond syndrome, who underwent successful related donor live transplant. Three pts died at d 165, 237 and 282 from resistant CMV, renal failure, and PCP respectively. This series suggests that an aggressive immunosuppressive conditioning regimen with partial T cell depletion results in successful engraftment and minimal GVHD in pediatric patients with SAA, even with HLA mismatched donors.