Fludarabine and Cyclophosphamide Based Conditioning Is Associated with Good Outcomes in Patients Undergoing Matched Sibling Donor Transplants for Aplastic Anaemia

Background: Fludarabine based conditioning protocols are increasingly being used for transplant (SCT) in patients with aplastic anaemia (AA) especially in those who have received multiple transfusions.

Patients and Methods: Between January 2004 and June 2019, 229 patients with AA and HLA identical sibling donors underwent SCT at CMC Vellore India using Fludarabine [180 mg/m² over 6 days] and Cyclophosphamide [120 mg/kg over 2 days]. Few patients received low dose ATG [ATGAM 40 mg/kg]. Data on HSCT and outcomes were collected from the institutional database and individual medical records.

Results: The median age was 23.9 years (range: 1.5 - 58) including 151 males and 78 females including 78 children (33.4%). Donors were matched sibling (n = 215) or family donors (n = 14). The graft source was Bone marrow in 11 and peripheral blood stem cells in 218. GVHD prophylaxis consisted mainly of cyclosporine and methotrexate mainly with few receiving post-transplant cyclophosphamide.

Engraftment occurred in 90% with graft failure in 2.6% and early death in 7.4%. Regimen related toxicity (RRT) was seen in 4.7% and included veno-occlusive disease of liver and hemorrhagic cystitis. Acute GVHD (grade 2-4) occurred in 26.4% while chronic GVHD was seen in 40.3%. The 5 year overall survival (OS) for the entire group is 75.9 + 4.9%. The 5 yr OS was 81.4 + 3.9% for ages 0 - 20, 76.3 + 4.4% for ages 21-40 and 55.3 + 9.3% for ages > 40 years. Age > 40 years (p = 0.000), presence of fever requiring hospital admission within 4 weeks prior to SCT (p = 0.001) and acute GVHD (p = 0.051) were identified as risk factors associated with a poor outcome on a univariate analysis while on a multivariate analysis, older age and fever continued to remain significant.

Conclusion: This is the largest series of patients with AA undergoing SCT using a fludarabine based conditioning and is associated with improved survival following sibling donor HSCT for AA. Presence of fever requiring a hospital admission immediately prior to SCT is associated with poor outcomes.