Abstract
Background:Hemopoietic stem cell transplantation (HSCT) remains the standard of care for eligible patients with acquired aplastic anemia (AA). Conditioning rfegimens have changed over the yearsAims:To asses the role of different conditioning regimens over the years in HSCT in patients with acquired AAMethods:We have analyzed the outcome of 179 patients with acquired aplastic anemia (AA) undergoing an HSCT in 3 consecutive eras: before year 2000, between 2001 and 2010 and beyond year 2010. The median age of the patients was 20,28,31 years in the three periods, and there has been an increased use of donors other than HLA identical siblings (6%, 45%, 62% respectively). The major change in the 3 periods, has been in the use of conditioning regimens: cyclophosphamide (CY) 200 mg/kg was used in 92%, 32% and 20% of patients respectively in the 3 periods; the combination of fludarabine (FLU), CY low dose (1200 mg/m^2) and total body irradiation 2 Gy (FLU‐LDCY‐TBI) was used in 5%, 58% and 20% of patients in the 3 periods; finally the combination of FLU CY 120 mg/kg and TBI 2 Gy (FLU‐CY‐TBI) was given to 0%, 9%, 58% of patients respectively. GvHD prophylaxis remained unchanged during the three transplant periods: cyclosporin methotrexate and ATG for all patients, with the addition of rituximab 200 mg on day+5, as of year 2002.Results:The 5 year survival has improved in three consecutive transplant eras, from 58% before year 2000, to 73% in the years 2001–2010, and 92% in the years 2011–2018.We then compared the outcome of transplants prepared with FLU‐LDCY‐TBI (n = 38) or with FLU‐CY‐TBI (n = 21): the 2 groups were comparable for patients age (31 years for FLU‐LDCY‐TBI, range 17–60, versus 39 years for FLU‐CY‐TBI, range 18–62, p = 0.2) and donor type (p = 0.2), with 44% and 55% of donors being unrelated. The 5 year survival was 62% for FLU‐LDCY‐TBI vs 95% for FLU‐CY‐TBI (p = 0.02). In the FLU‐LDCY‐TBI, 4 patients died of graft failure (11%), 7 died of infections (18%) and 3 (8%) of toxicity. In the FLU‐CY‐TBI, 1 patient died of rejection (4%) and 1 of GvHD (4%). No patient experience EBV‐driven post transplant lymphoproliferative disorders (PTLD)Summary/Conclusion:In conclusion CY200 mg/kg remains standard of care for young patients grafted from identical siblings. The combination of FLU‐CY 120 mg/kg and TBI2 Gy appears to allow a better engraftment as compared to FLU‐LDCY‐TBI, and may be preferred for older patients and patients grafted from unrelated donors. We recommend low dose rituximab on day+5, which will effectively prevent PTLD.
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