Risk factors affecting outcome of second HLA-matched sibling donor transplantations for graft failure in severe acquired aplastic anemia

Abstract

We examined transplantation outcomes after a second HLA-matched sibling transplantation for primary (16%) or secondary (84%) graft failure in 166 patients with severe acquired aplastic anemia (AA). Two-thirds of these patients has a performance score < 90. In most cases (88%), the same donor was used for both transplants, for both transplantations, and 84% of the second transplantations used bone marrow grafts. We identified 2 prognostic factors: intertransplantation interval (surrogate for primary graft failure and early secondary graft failure) and performance status. Shorter intertransplantation interval (<or= 3 months) and poor performance score (< 90) at second transplantation were associated with high mortality. In patients with a performance score of 90% to 100%, the 8-year probability of overall survival (OS) after second transplantation <or= 3 and > 3 months from first transplantation was 56% and 76%, respectively. The corresponding probabilities in patients with lower performance scores were 33% and 61%. The predominant cause of failure after second transplantation was nonengraftment (in 72 of 166 patients), most commonly in patients with primary or early secondary graft failure (51 of 72; 71%). Our data indicate that novel approaches, including conditioning regimens with greater immunosuppression, should be explored for these patients.

Figure 1

Cumulative incidence of neutrophil and platelet recovery after second HLA-matched sibling donor transplantation for graft failure.

Figure 2. Overall Survival after second HLA-matched sibling donor transplantation for graft failure in severe aplastic anemia by time from first to second transplant and karnofsky performance score

Eight-year probabilities of overall survival are as follows: a) Probability of performance scores of 90–100, when the interval between the first and second transplant was beyond 3 months was 76% (95% CI 62 – 88). b) Probability of performance scores of <90, when the interval between the first and second transplant was beyond 3 months was 61% (95% CI 50 – 72). c) Probability of performance scores of 90–100, when the interval between the first and second transplant was within 3 months was 56% (95% CI 24 – 85). d) Probability of performance scores of <90, when the interval between the first and second transplant was within 3 months was 33% (95% CI 19 – 49).