Allogeneic stem cell transplantation for severe acquired aplastic anaemia using a fludarabine‐based preparative regimen

Abstract

SummaryWe reviewed our experience in the treatment of 13 patients with severe acquired aplastic anaemia, using a newly developed non-myeloablative regimen consisting of fludarabine (total dose 180 mg/m 2 ), cyclophosphamide (total dose 120 mg/kg), and antithymocyte globulin (total dose 40 mg/kg). All except one patient received multiple transfusions and had failed prior immunosuppressive treatment. Twelve out of 13 patients achieved sustained engraftment. One patient was not evaluable for engraftment because of early death on day +10. None of the patients developed graft failure. Mucositis of mild-to-moderate severity was the only observed regimen-related toxicity. The cumulative incidence of acute graft-versus-host disease (GvHD) grade II-IV and III-IV was 8AE3% and 0%, respectively. With a median follow-up period of 45 months, the 5-year overall survival probability was 84%. Eight out of 11 surviving patients have been followed for more than 1 year and only one developed limited chronic GvHD. All patients enjoy a normal life style, with a Karnofsky score of 100%, and all except three, followed for 3, 5 and 6 months respectively, are free of any immunosuppressive medication. The results of this study look promising, while prospective clinical trials may be required to confirm the benefits of this regimen as an alternative to existing protocols.

Improved outcome of patients older than 30 years receiving HLA-identical sibling hematopoietic stem cell transplantation for severe acquired aplastic anemia using fludarabine-based conditioning: a comparison with conventional conditioning regimen

“…17 These results reinforce encouraging survival estimates observed in previously reported studies without a comparative group, using such Flu-based regimens independently of patient age. [13][14][15][16] In older patients, the comparison of Flu-based to standard HSCT will certainly need to be further evaluated in a still larger number of patients to allow a definitive conclusion to be drawn.…”

“…8,9 Such Flu-based regimens have been explored in various nonmalignant diseases without conferring a significant survival advantage when compared to conventional myeloablative regimens. 10 In patients with SAA specifically, several previous case reports 11,12 or non-comparative studies [13][14][15][16] have reported encouraging results in the setting of HLA-matched related HSCT. The EBMT SAA working party has recently reported a favorable experience using Flu-based HSCT in SAA patients transplanted with unrelated (n=33) or family mismatched (n=5) donors.…”

Implications of CD34+ cell dose on clinical and haematological outcome of allo-SCT for acquired aplastic anaemia

“…5,6,[17][18][19] Other published studies to date have not included CD34 þ cell dose in their analysis. [20][21][22][23][24] We used the median CD34 þ count to define the cutoff to ensure an even distribution of patients in the low-and high-dose arms.…”

Impact of age on outcomes after bone marrow transplantation for acquired aplastic anemia using HLA-matched sibling donors

“…The observed disadvantage with busulfan plus cyclophosphamide and fludarabine-containing regimens contrasts with reports of successes with busulfan and fludarabinecontaining regimens. 12,[22][23][24][25] Most of these reports included relatively few patients and none compared the various regimens directly. More definitive studies are, therefore, needed before widespread adoption of conditioning regimens other than cyclophosphamide plus anti-thymocyte globulin.…”