Unrelated donor search and unrelated donor transplantation in the adult aplastic anaemia patient aged 18–40 years without an HLA-identical sibling and failing immunosuppression

Abstract

Currently at least 75% of patients with severe aplastic anaemia can be successfully transplanted using a matched unrelated donor (UD) haematopoietic SCT (HSCT). For children, outcomes are similar to matched sibling donor (MSD) HSCT. This improvement in outcome over time is likely due to improved HLA tissue typing to identify better matched donors, improvements in the conditioning regimen, particularly fludarabine-based regimens, and improved supportive care. Graft rejection occurs in B15% of adults, but is less frequent in children. Chronic GVHD remains a concern but may be reduced by using Alemtuzumab instead of ATG. UD HSCT should be considered early after failure to respond to one course of immunosuppressive therapy, but for children who lack a MSD up front matched UD HSCT may be considered. (2013) 48, 198-200; doi:10.1038/bmt.2012.233; published online 26 November 2012 Bone Marrow TransplantationKeywords: aplastic anaemia; HSCT The outcome of unrelated donor (UD) transplants for patients with aplastic anemia (AA) has improved in the last decade. 1,2 Better selection of HLA-matched donors has probably had a major role, but also significant changes in the conditioning regimen have occurred, including the use of fludarabine (FLU)-based conditioning, the addition of low-dose (2 Gy) 3-6 TBI in adults, and the use of Alemtuzumab as an alternative to ATG. 7-10 OS is currently 475%. 6,10 Results of UD transplants have improved to such an extent that treatment recommendations should be adapted: UD transplantation is now considered after failure to respond to one course of immunosuppressive therapy, and in children UD haematopoietic SCT (HSCT) may be considered as first line treatment in severe aplastic anaemia (SAA). 11 Centres match either for A, B, C and DRB1 at the allelic level, looking for 8/8 matched donors 12 or for DQ looking for a 10/10 match. In a recent European BMT (EBMT) analysis, we showed an effect of mismatching (o8/8 vs 8/8 match) only for patients prepared with FLU-CY and ATG (FCA), but not for patients receiving FCA supplemented with low-dose TBI 2 Gy (FCA-TBI). 13 In general, an 8/8 (A, B, C and DRB1) matched donor would be ideal, but a 7/8 (or 9/10) match would probably be also acceptable if low-dose TBI is used. [14][15][16] The combination of FLU-CY and ATG is used most often for the conditioning regimen in UD HSCT for acquired AA, 5,6 although Alemtuzumab is an emerging alternative option to ATG (FCC). 7-10 Low-dose TBI, 2 or 3 Gy, was added following the Japanese and USA studies. 3,4 The dose of CY was originally set at 300 mg/ m 2  4. 5,6 This was associated with a significant risk of rejection, so the current indication is to increase the dose of CY to 120 mg/kg. The working party SAA currently recommends FLU 30 mg/m 2  4, CY 30 mg/kg  4 and ATG. TBI (2 Gy) can be added on day À 1 for patients aged 414 years, 6 but can be considered also for children sensitized after numerous blood transfusions. Alemtuzumab used with FLU and CY 300 mg/m 2  4 (FCC) has recently been reported to show enco...

Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia

“…Recently, the outcomes of unrelated or mismatched-related donor transplantation for treating AA patients has improved significantly, and an OS in the range of 70-80% is anticipated for selected patients. 27,28 In particular, the best results are achieved for young patients with disease duration of less than one year. 29 Indeed, the EBMT group reported that up-front matched or mismatched unrelated donor HSCT has similar outcome to matched sibling donor HSCT in idiopathic severe AA of childhood and adolescence.…”

Biomarkers for predicting clinical response to immunosuppressive therapy in aplastic anemia

“…Recently, the outcomes of unrelated and mismatchedrelated donor transplantation in AA patients have improved dramatically, with an OS in the range of 70-80 % expected in selected patient populations [38,39]. In particular, young patients with disease duration of <1 year have achieved better results than adults did [40].…”

Current outcome of HLA identical sibling versus unrelated donor transplants in severe aplastic anemia: an EBMT analysis

“…1 Transplantation from an unrelated donor (UD) is usually considered after failure of at least one course of IST. 2 This strategy is based on a relatively high risk of complications for UD transplant recipients, such as graft rejection, graft-versus-host disease (GvHD) and infections. [3][4][5] However, things have changed in recent years, and the outcome of unrelated donor transplants has significantly improved.…”